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Improper installation of SKSE64 – This might be a common problem for most Skyrim SE users who have recently applied SKSE 64.

Antivirus – If you have any third-party security software running, it might label Skyrim and its game files as a threat, and will prevent it from launching properly.

This includes the SKSE64 script extender, which will lead to an error.

Windows Firewall – Some of Skyrim’s processes might be blocked by Windows Firewall upon launch.

This folder also contains main Windows files, which might prevent it from running as a safety precaution.

Permissions – Your Steam, as well as Steam apps, will be installed by default on your computer’s Program Files folder.

What Causes the Skyrim SKSE64 Not Working error?

2.5 Fix #5: Disable Auto-Updates from Steam.

2.3 Fix #3: Add both Skyrim apps and Steam to Exclusions on Windows Defender.

2.2 Fix #2: Grant Windows Defender Firewall access.2.1 Fix #1: Install Steam and its Apps outside of C: \Program Files\.2 How to Fix the SKSE64 Not Working error in Skyrim?.1 What Causes the Skyrim SKSE64 Not Working error?.