Detectives believe a 55-year-old man shot a 40-year-old woman before killing himself.
It happened just before 5.30 p.m. at the University Inn, located across from Fresno State. Investigators say the two were in a relationship.
"It was a lovers quarrel, romance was involved, we are not sure what it was about," said Fresno police Lt. Joe Gomez.
Police say although the woman was bleeding, she was able to call the hotel's front desk. Staff members there then called 911.
The woman was rushed to Community Regional Medical Center where she went into surgery. She was last listed in critical but stable condition.
Officers do not believe anyone else is in danger, but people checking into the hotel are now worried about their own safety.
"It's pretty scary running up to a shooting," said Ruben Gaduno.
The names of the suspect and victim have not been made available. The incident remains under investigation.