The D-backs aren't sure whether Upton injured his oblique or rib cage -- he's listed as day-to-day at this point -- but either way, he will likely be out of the lineup when the two teams meet in Thursday's rubber match.
"It certainly could be a DL, not sure, we'll know more tomorrow," Arizona manager Bob Melvin said of Upton's injury.
"It's just stiff now," Upton said after the game. "We'll see how it is.
Upton wasn't the only person to experience frustration on Wednesday. Starting pitcher Micah Owings (6-8) is still trying to recapture the form that allowed him to start the season 6-2.
Owings clearly didn't have his best command in this one, as he walked five and hit three batters. That allowed the Nationals to deal him his sixth straight loss, despite only getting one hit against the right-hander.
"Obviously, I wasn't sharp," Owings said. "I just kept fighting. I'm going to keep working because I've got it, I know I've got it."
After a 1-2-3 first, the Nats were able to push across a run in the second when Owings allowed a one-out single before hitting Ronnie Belliard and Paul Lo Duca to load the bases. Kory Casto then drew a walk to force in a run.
"Not his best command at times, but fought very hard," Melvin said of Owings. "He competed pretty hard. He wasn't giving up many hits and when he had to make a pitch, he did."
Indeed, Owings continued to pitch himself into, and out of, trouble until the sixth, when he finally ran out of gas.
With one out in the inning, Owings walked Dmitri Young and after he got Belliard to pop out, he walked Lo Duca. At that point, pitching coach Bryan Price went to the mound to talk to Owings and the right-hander told him he had nothing left in the tank.
Connor Robertson came on in relief, but didn't provide much, as he allowed a run-scoring double to Casto, and Jesus Flores all but put the game on ice when he followed with a three-run shot into the D-backs' bullpen in left to give the Nats a 5-0 lead.
It was Owings' first start since June 27, when he strained his gluteus mucscle. He missed his next start and threw once in relief for the D-backs before Wednesday.
"I'm not going to go there," Owings said when asked if the layoff may have affected him. "I don't think too much about that, because last year I got skipped a couple of times and came right back out and got my job done and helped the team out."
Once again the D-backs struggled on offense, managing just three hits.
Nationals starter John Lannan (5-9) allowed two hits and walked three in six innings before turning things over to the bullpen.
"It was pretty frustrating," Melvin said. "All our guys are frustrated. You've got to obviously give credit to Lannan, but we couldn't seem to get decent swings, let alone decent at-bats tonight."