Yadier Molina blasted a three-run homer in the first inning for the decisive hit that led to the Cardinals taking the first two of three in the series, which wraps up on Wednesday.
"We had good at-bats today," Guillen said. "That's a good sign. Either way, no matter how you swing the bat or pitch, it's another loss. At the end of the day, all that really matters is winning."
The Marlins dropped to 34-40, going six under .500 for the first time since being 8-14 on April 30.
Guillen, angered at home-plate umpire Dan Bellino's strike zone, was ejected for the first time as Miami's manager. It was the 28th time in his career he's been tossed.
Giancarlo Stanton belted his 17th home run, a mammoth blast off Lohse in the first inning. But the Marlins stumbled for the second straight night, falling to 5-18 in June.
It was a tale of two games for Zambrano. The right-hander overcame a 37-pitch first inning to get through 6 2/3, throwing 125 pitches -- the most by a Marlins starter since Anibal Sanchez threw 125 on June 15, 2011, against the Phillies.
"I work hard to throw a lot of pitches," Zambrano said. "The most important thing is to go out there, and if you give up five runs or whatever, and you still can go into the seventh inning, that's pretty good. We lost the game, and [that's] the most painful thing, you know."
Zambrano lost to the Cardinals for the first time since Sept. 19, 2008.
The last pitch Zambrano threw was a borderline full-count pitch to Allen Craig, ruled ball four by Bellino. As Guillen made his way to the mound to replace his veteran starter, he shouted some words at Bellino, who promptly ejected the fiery manager.
"I think after I saw the replay, I was wrong," Guillen said. "After I saw the replay, that ball was close. I looked at it very well. From the dugout, I thought it was a better pitch. Buck was talking to him. To see Carlos' reaction, I thought that ball was closer than what it was.
"At least I'm honest and I take my responsibility. I think the heat of the game put me in that position."
Before leaving the field, Guillen gave Bellino an earful.
Asked what he told the umpire, the Venezuela-born manager said, "I don't think he understood what I said. He was looking at me like an alien or something. ... I think I was wrong, but I have to protect my ballplayers."
After allowing at least one run in four straight innings in Monday's 8-7 loss in 10 innings, the Marlins watched the Cardinals waste little time in getting on the board on Tuesday, seizing control in the first and not needing any additional support.
"We made two errors," Guillen said. "Carlos was very inconsistent in the strike zone. Obviously, when you make mistakes and Mr. Molina comes up to the plate, you're in a dangerous situation. The first inning was like a carryover from last night's game. Thank goodness we stopped it right there. We got better, pitched better."
Rafael Furcal singled to open the inning, and with one out, Zambrano threw Matt Holliday's comeback grounder into center field, putting runners on the corners.
"I was too quick to second base and threw the ball into center field," Zambrano said. "But I was able to pitch through six innings and save the bullpen. Our bullpen has pitched a lot lately. As a veteran, I think I have to be focused and throw the ball right and secure one out. Whatever happens, happens. It was my fault."
Carlos Beltran slapped an RBI single, and Craig ripped a hard grounder that Jose Reyes couldn't handle at short for the second error of the inning.
"That's right in front of me," Reyes said. "At least do a better job keeping the ball in front of me. It wasn't easy. It wasn't that hard either. Big inning right there.
"Zambrano kept us in the game. We weren't able to score any runs. We scored two runs. That's not going to get it done."
Molina, who belted a two-run, game-tying homer in the ninth inning on Monday, crushed a three-run shot to left.
In the bottom of the first, Stanton launched his 454-foot shot off Lohse, who gave up two runs in 7 1/3 innings. In the fourth, Stanton's double set up Miami's second run. He scored on Greg Dobbs' sacrifice fly, making it 5-2.
The Marlins were set up for a potential big inning in the sixth, but Furcal made a dazzling scoop on a short-hopped liner and turned a double play on Logan Morrison. Reyes, who doubled, was stranded at third.
"The reason I got released from the Atlanta Braves was because of him," Guillen said. "They released me so Furcal can get a chance. Furcal is a tremendous shortstop. He came out to be a great player. That play, it meant a lot in the game. If that's a base hit, maybe it's a different ballgame."