diff --git a/CHANGES.md b/CHANGES.md
index 56f7b7b..db752b5 100644
--- a/CHANGES.md
+++ b/CHANGES.md
@@ -4,6 +4,7 @@
 
 - Add Renode device support.
 - Refuse commands longer than the target CONFIG_LINE_MAX.
+- Reopen serial ports that disappear on target reset (USB re-enumeration).
 
 ## 0.0.3
 
diff --git a/src/ntfc/device/serial.py b/src/ntfc/device/serial.py
index 808bb98..5e7c107 100644
--- a/src/ntfc/device/serial.py
+++ b/src/ntfc/device/serial.py
@@ -43,6 +43,7 @@ def __init__(self, conf: "CoreConfig"):
         """Initialize sim emulator device."""
         DeviceCommon.__init__(self, conf, echo=False)
         self._ser = None
+        self._lost = False
 
     def _decode_exec_args(self, args: str) -> Dict[str, Any]:
         """Decode a serial port configuration string."""
@@ -87,8 +88,41 @@ def _decode_exec_args(self, args: str) -> Dict[str, Any]:
         except Exception as e:
             raise ValueError(f"Invalid format '{args}': {e}") from e
 
+    def _open(self) -> None:
+        """Open the serial port."""
+        path = self._conf.exec_path
+        args = self._conf.exec_args
+
+        if args:  # pragma: no cover
+            self._ser = serial.Serial(
+                path, timeout=0, **self._decode_exec_args(args)
+            )
+        else:
+            self._ser = serial.Serial(path, timeout=0)
+
+    def _port_lost(self) -> None:
+        """Drop a port that failed, e.g. a USB device re-enumerating."""
+        logger.info("serial port lost, reopening")
+
+        assert self._ser
+        self._ser.close()
+        self._ser = None
+        self._lost = True
+        self._reopen()
+
+    def _reopen(self) -> None:
+        """Try to reopen a lost port."""
+        try:
+            self._open()
+            self._lost = False
+        except serial.SerialException:
+            self._ser = None
+
     def _dev_is_health_priv(self) -> bool:
         """Check if the serial device is OK."""
+        if not self._ser and self._lost:
+            self._reopen()
+
         if not self._ser:
             return False
 
@@ -101,19 +135,23 @@ def _write(self, data: bytes) -> None:
 
         assert self._ser
 
-        if self._conf.line_buffered:
-            if data[-1] != ord("\n"):
-                data += b"\n"
-
-            self._ser.write(data)
-        else:
-            # send char by char to avoid line length full
-            for c in data:
-                self._ser.write(bytes([c]))
-
-            # add new line if missing
-            if data[-1] != ord("\n"):
-                self._ser.write(b"\n")  # pragma: no cover
+        try:
+            if self._conf.line_buffered:
+                if data[-1] != ord("\n"):
+                    data += b"\n"
+
+                self._ser.write(data)
+            else:
+                # send char by char to avoid line length full
+                for c in data:
+                    self._ser.write(bytes([c]))
+
+                # add new line if missing
+                if data[-1] != ord("\n"):
+                    self._ser.write(b"\n")  # pragma: no cover
+        except (serial.SerialException, OSError):
+            self._port_lost()
+            return
 
         # read all garbage left by character echo
         _ = self._read_all(timeout=0)
@@ -136,22 +174,20 @@ def _read(self) -> bytes:
 
         assert self._ser
 
-        return self._ser.read(size=1024)
+        try:
+            return self._ser.read(size=1024)
+        except (serial.SerialException, OSError):
+            self._port_lost()
+            return b""
 
     def _start_impl(self) -> None:
         """Start serial communication implementation."""
-        timeout = 0
-        path = self._conf.exec_path
-        args = self._conf.exec_args
+        logger.info(f"serial path: {self._conf.exec_path}")
+        logger.info(f"serial args: {self._conf.exec_args}")
 
-        logger.info(f"serial path: {path}")
-        logger.info(f"serial args: {args}")
-
-        if args:  # pragma: no cover
-            args = self._decode_exec_args(args)
-            self._ser = serial.Serial(path, timeout=timeout, **args)
-        else:
-            self._ser = serial.Serial(path, timeout=timeout)
+        # A USB port may show up only after the device boots
+        self._lost = True
+        self._reopen()
 
         # reboot device if possible
         self.reboot()
@@ -177,6 +213,7 @@ def _stop_impl(self) -> None:
         if self._ser:  # pragma: no cover
             self._ser.close()
             self._ser = None
+        self._lost = False
         logger.info("serial device closed")
 
     def _poweroff_impl(self) -> bool:
diff --git a/tests/device/test_serial.py b/tests/device/test_serial.py
index b08c56d..11f577f 100644
--- a/tests/device/test_serial.py
+++ b/tests/device/test_serial.py
@@ -123,8 +123,8 @@ def test_device_sim_init(serial_config, serial_pair):
 
     ser = DeviceSerial(serial_config)
 
-    # no path and args
-    with pytest.raises(serial.serialutil.SerialException):
+    # no port yet (USB device not enumerated): wait for boot, then time out
+    with pytest.raises(TimeoutError):
         serial_config._config["exec_path"] = ""
         serial_config._config["exec_args"] = ""
         ser.start()
@@ -191,3 +191,38 @@ def fake_wait(timeout=5):
 
     # boot wait uses the configured boot_timeout
     assert boot_timeouts == [9]
+
+
+def test_device_serial_reconnect(serial_config, serial_pair):
+
+    serial_config._config["exec_path"] = serial_pair[1]
+    ser = DeviceSerial(serial_config)
+    ser._open()
+    first = ser._ser
+
+    # a failed read (USB device gone) reopens the port
+    def fail(*args, **kwargs):
+        raise serial.SerialException("device disconnected")
+
+    ser._ser.read = fail
+    assert ser._read() == b""
+    assert ser._ser is not None
+    assert ser._ser is not first
+    assert ser._lost is False
+
+    # a failed write while the port is still missing leaves it lost
+    serial_config._config["exec_path"] = "/dev/ntfc-no-such-port"
+    ser._ser.write = fail
+    assert ser._write(b"a") is None
+    assert ser._ser is None
+    assert ser._lost is True
+    assert ser._dev_is_health_priv() is False
+
+    # the health check reconnects once the port is back
+    serial_config._config["exec_path"] = serial_pair[1]
+    assert ser._dev_is_health_priv() is True
+    assert ser._lost is False
+
+    ser.stop()
+    assert ser._lost is False
+    assert ser.notalive is True