In the middle level of the Sewers, south of the Treatment Pool Room you will see a safe sitting on a table. You can open this safe by using a classic right left three number combination. You will learn the combination to the safe if you are observant or if you read the letter items found throughout the world as they reveal that the safe’s code is written on the side of it.
If you are in front of the safe, if you look on the right side of it you will see the code written in chalk. The code for the sewer safe is Left 2, Right 12, Left 8
The Sewer Safe Code is Left 2, Right 12, Left 8
In Leon’s playthrough the reward for opening the safe is a new stock for the W-870 shotgun. This item is another upgrade to the shotgun that continues to make it a more powerful weapon. At this point in the Sewers with Leon you should have access to the standard pistol, the shotgun, the magnum gun, and the chemical flamethrower.
There are no prerequisites to opening the Sewer Safe. As soon as you make it to this area you can unlock it and upgrade the shotgun. You will encounter some stronger enemies in this area so an upgraded weapon will certainly help out somewhat while exploring the Sewer and attempting to solve the Chess Piece Plug Puzzle.