The shooting happened at 12:08 a.m. at 1655 N. Crescent Heights Blvd. near Marley Drive, according to the Los Angeles Police Department.
Police said the mansion appears to be a rental home, possibly an Airbnb, that was rented out by people from Chicago for the big football event.
The party was apparently in full swing until two groups of men got into a fight, officials said, which led up to the shooting.
A 26-year-old man and a 27-year-old man were taken to a hospital for treatment. One man was hit in the back and apparently in critical condition, while the other victim was shot in the lower back. He was alert and speaking, according to police.
Two men have since been detained by the LAPD for further questioning.
Sources told FOX 11 the partygoers weren't too cooperative in discussing who the shooters were with police.
City News Service contributed to this report.