Luis Sera is a native of the Spanish village featured in Resident Evil 4. After returning from Madrid, where he pursued a career in the police force, Luis was hired by Osmund Saddler as a researcher for the Las Plagas parasite, experimenting with it to enhance the abilities of the host it infected. After some time, Luis became dissappointed of Saddler's intentions, and he betrayed Saddler by stealing a Plaga sample. Saddler discovered him, and ordered for him to be tied up inside a closet, waiting for his fate.
Leon S. Kennedy found Sera, and freed him, making Luis his ally. Luis helps Leon finding Ashley Graham, and assists them in escaping Spain, as well as avoiding the Plaga parasite to grow inside Leon.
Inside Ramon Salazar's castle, Luis manages to reunite with Leon and Ashley. Just before giving Leon the Plaga sample, Saddler impales him through the chest and takes back the sample. In his dying breath, Luis gives Leon some pills to slow down the growth of the parasite, giving him some time to find a way to stop the virus completely (i.e. a plaga-removing machine Luis invented).
Throughout the rest of the game, Leon can find Luis's research notes scattered in the island, giving him information about the parasite and the Ganados Leon will find.
It is suspected that Luis was in league with Ada Wong, helping her to investigate the Los Illuminados cult.
In Resident Evil 4, it is possible for Luis to kill Leon. During Chapter 2-3 when Leon, Ashley, and Luis are trapped inside a house and are forced to fight for survival against the Ganados; if Leon shoots Luis a couple of times, Luis will turn around and say "Adios Leon" and shoot back, resulting in Leon's death.