Yes, you can almost always check out of a hotel at 4:00 AM, especially in larger chains or airport hotels that staff their front desks 24/7. If you are staying at a smaller boutique hotel or a bed-and-breakfast, it is a good idea to inform the staff the night before so they can finalize your bill and ensure you have a clear path to exit. Most modern hotels also offer "Express Check-out" options, such as dropping your keys in a designated box in the lobby or checking out via a mobile app, which eliminates the need to speak with anyone at that early hour. If you have a pre-paid room, you can simply leave your keys in the room and walk out, though stopping at the desk (or checking the app) is safer to ensure no unexpected "minibar" or "service" charges have been added to your final statement. If you need a taxi or a wake-up call for your early departure, the front desk can usually arrange those services for you the previous evening to ensure a stress-free start to your travel day.