diff --git a/src/debugpy/server/cli.py b/src/debugpy/server/cli.py
index aa506e0c..1eede7d0 100644
--- a/src/debugpy/server/cli.py
+++ b/src/debugpy/server/cli.py
@@ -340,6 +340,14 @@ def start_debugging(argv_0):
     os.environ["DEBUGPY_RUNNING"] = "true"
 
 
+def _skip_sys_path_prepend():
+    # Python does not prepend the script's parent directory (for a file target)
+    # or the current directory (for -m / -c) to sys.path in isolated mode (-I) or
+    # safe-path mode (-P / PYTHONSAFEPATH), so debugpy shouldn't either.
+    # `sys.flags.safe_path` was added in Python 3.11; fall back to False on older versions.
+    return sys.flags.isolated or getattr(sys.flags, "safe_path", False)
+
+
 def run_file():
     target = options.target
     start_debugging(target)
@@ -348,10 +356,13 @@ def run_file():
     # if the target is a file (rather than a directory), it does not add its
     # parent directory to sys.path. Thus, importing other modules from the
     # same directory is broken unless sys.path is patched here.
+    # In isolated / safe-path mode, Python itself doesn't add the script directory,
+    # so don't do it here either.
 
     if target is not None and os.path.isfile(target):
-        dir = os.path.dirname(target)
-        sys.path.insert(0, dir)
+        if not _skip_sys_path_prepend():
+            dir = os.path.dirname(target)
+            sys.path.insert(0, dir)
     else:
         log.debug("Not a file: {0!r}", target)
 
@@ -362,9 +373,11 @@ def run_file():
 
 
 def run_module():
-    # Add current directory to path, like Python itself does for -m. This must
-    # be in place before trying to use find_spec below to resolve submodules.
-    sys.path.insert(0, str(""))
+    # Add current directory to path, like Python itself does for -m, unless
+    # it's suppressed by isolated / safe-path mode. This must be in place before
+    # trying to use find_spec below to resolve submodules.
+    if not _skip_sys_path_prepend():
+        sys.path.insert(0, str(""))
 
     # We want to do the same thing that run_module() would do here, without
     # actually invoking it.
@@ -396,8 +409,10 @@ def run_module():
 
 def run_code():
     if options.target is not None:
-        # Add current directory to path, like Python itself does for -c.
-        sys.path.insert(0, str(""))
+        # Add current directory to path, like Python itself does for -c,
+        # unless it's suppressed by isolated / safe-path mode.
+        if not _skip_sys_path_prepend():
+            sys.path.insert(0, str(""))
         code = compile(options.target, str("<string>"), str("exec"))
 
         start_debugging(str("-c"))
diff --git a/tests/debugpy/test_cli_args.py b/tests/debugpy/test_cli_args.py
index e7a55d5e..5b7893ec 100644
--- a/tests/debugpy/test_cli_args.py
+++ b/tests/debugpy/test_cli_args.py
@@ -2,6 +2,12 @@
 # Licensed under the MIT License. See LICENSE in the project root
 # for license information.
 
+import os
+import subprocess
+import sys
+
+import pytest
+
 from tests import debug
 
 
@@ -33,3 +39,59 @@ def code_to_debug():
         cli_options = backchannel.receive()
         assert cli_options['mode'] == 'connect'
         assert cli_options['target_kind'] == 'file'
+
+
+@pytest.mark.parametrize("target_kind", ["file", "module", "code"])
+@pytest.mark.parametrize("python_flag", ["-I", "-P"])
+def test_safe_sys_path_modes(pyfile, tmpdir, target_kind, python_flag):
+    # In isolated mode (-I) and safe-path mode (-P / PYTHONSAFEPATH), Python does
+    # not prepend the script directory (for a file target) or the current directory
+    # (for -m and -c) to sys.path, and neither should debugpy.
+    # https://github.com/microsoft/debugpy/issues/1916
+    if python_flag == "-P" and sys.version_info < (3, 11):
+        pytest.skip("-P / PYTHONSAFEPATH requires Python 3.11+")
+
+    import debugpy
+
+    @pyfile
+    def code_to_debug():
+        import sys
+
+        print(repr(sys.path[0]))
+
+    debugpy_root = os.path.dirname(os.path.dirname(os.path.abspath(debugpy.__file__)))
+
+    code = "import sys; print(repr(sys.path[0]))"
+    cli_args = ["--listen", "127.0.0.1:0"]
+    if target_kind == "file":
+        cli_args += [code_to_debug.strpath]
+        not_expected = os.path.dirname(code_to_debug.strpath)
+    elif target_kind == "module":
+        tmpdir.join("debuggee_module.py").write(code)
+        cli_args += ["-m", "debuggee_module"]
+        not_expected = ""
+    else:
+        cli_args += ["-c", code]
+        not_expected = ""
+
+    # -I / -P do not block explicit sys.path edits, so make debugpy (and the module
+    # target) importable by inserting their locations before invoking the CLI, the
+    # same way they would be resolved from site-packages of an installed copy.
+    wrapper = (
+        "import sys; "
+        "sys.path.insert(0, {tmpdir!r}); "
+        "sys.path.insert(0, {debugpy_root!r}); "
+        "sys.argv[1:] = {cli_args!r}; "
+        "from debugpy.server import cli; cli.main()".format(
+            tmpdir=tmpdir.strpath, debugpy_root=debugpy_root, cli_args=cli_args
+        )
+    )
+
+    output = subprocess.check_output(
+        [sys.executable, python_flag, "-c", wrapper],
+        cwd=tmpdir.strpath,
+        stderr=subprocess.DEVNULL,
+    )
+
+    sys_path_0 = output.decode("utf-8").strip().splitlines()[-1]
+    assert sys_path_0 != repr(not_expected)