According to the California Highway Patrol, at about 11:30 p.m., Mathews was traveling southbound on Sports Arena Boulevard to eastbound Interstate 8 when he lost control of his 2010 BMW M6 and struck another vehicle.
Mathews was taken to the hospital after complaining of pain. The occupants of the other vehicle were not hurt, the CHP said.
The CHP said Mathews, 24, may have been driving too fast before the crash, but the exact cause remains under investigation.
CHP officials told 10News they did not feel the need to give Mathews a sobriety test because he did not look to be under the influence of drugs or alcohol.
"I was heading to the hotel and basically I come around the corner I take every day to come to work and I felt the car start to drift and I overcompensated and spun out and got hit by another car, but thankfully everybody's OK and, you know, I'm good to go," Mathews said.
Mathews sat out Tuesday's afternoon practice and told reporters he's not sure if he'll practice on Wednesday. He told the media he banged up his elbow a little bit in the crash, but said he would be fine.
"When he's ready to go, he's going to go and that's a day-to-day thing," said Chargers head coach Norv Turner.
Chargers Director of Public Relations Bill Johnston confirmed Mathews was "just a little shaken up" due to the crash, but declined to comment further.
Mathews made the 2011 Pro Bowl squad after rushing for 1,091 yards and six touchdowns. He also caught 50 passes for 455 yards.
Mathews was the team's first-round draft pick in 2010 out of Fresno State.