The Chargers, having claimed a dramatic win over the Arizona Cardinals in Week 12, bumped back down to earth with a 27-20 loss at Allegiant Stadium.
It leaves the Chargers 6-6 and a game adrift of the New York Jets in the final Wild Card place in the AFC playoff picture.
They now face a critical home game with the 8-4 Miami Dolphins, and safety James believes they can ill-afford any further slip-ups if they are to make the playoffs for the first time since 2018.
"We gotta keep playing. There's more games to be played. Prime time next week. We gotta come out [with a] sense of urgency," said James.
"Each game from here on out, we can't lose anymore. We gotta win out."
The Chargers' run defense was again a problem area for Los Angeles, allowing Josh Jacobs to rush for 144 yards and a second-quarter touchdown.
Los Angeles' defense is allowing 5.43 yards per rush in 2022, the most in the NFL, and head coach Brandon Staley blamed poor tackling for their struggles.
"I thought we played well early," Staley said of their efforts to stop Jacobs.
"I thought there were some missed tackles in the second half, which led to most of his yards. I thought we were in good run structures but missing tackles. He forces people to miss.
"No one is out there trying to miss. He's a good back and that's going to happen. I really felt like we defended well in the first half outside of a couple of misses. In the second half, it was a little up and down.
"Guys just have to tackle better."