Lost in Nightmares is the first story-based DLC for Resident Evil 5, set during a previous mission hinted at in flashback from that game. It is about 1 hour in length, depending on the difficulty, and experienced players can beat it in under 30 minutes. It is, all together, one chapter filled with classic puzzles and moments that will take players back to the first Resident Evil. It also features a scoreboard with worldwide rankings based on performance in the scenario as well as collection items.

This extra chapter is not accessible from the start of the game. It becomes unlocked after Chapter 3-1, the Marshlands, has been completed in the core campaign.