The A's rallied for three runs in the bottom of the ninth off Qualls, winning the game on a walk-off RBI single by Josh Reddick, to send the Astros to their sixth consecutive loss, 4-3, at sunny O.co Coliseum.
"It's a tough loss, especially playing as well as we played leading up to that ninth inning," Astros manager Bo Porter said. "We didn't close it out."
The blown save was the second in four games for the Astros, who made beefing up their bullpen a priority in the offseason, with the acquisitions of Qualls, Matt Albers, Anthony Bass and Jesse Crain, who is on the disabled list. Houston blew a league-high-tying 29 saves last year.
The Astros have been using a closer-by-committee setup this season, with Qualls getting his shot Saturday. He's certainly no stranger to the role, having saved 36 games in a two-year span with Arizona in 2009-10.
It was his first game action in more than a week. He had spent all day Wednesday at home in Houston ill, and was still regaining his strength upon arriving in Oakland early Friday. It was the same sickness that afflicted several of his teammates, including Saturday's starter Brett Oberholtzer.
"It's frustrating, especially for me," Qualls said. "We had a chance to win the game and [Oberholtzer] pitched his heart out and he's been battling sickness as well and he did a hell of a job. To come away with nothing and to have them celebrate on the field is not a good feeling."
Qualls started the ninth with a 3-1 lead, and promptly gave up a solo homer to Jed Lowrie, whom he had never faced. The next two batters reached on Josh Donaldson's walk and Yoenis Cespedes' single. Qualls recovered to strike out John Jaso before Alberto Callaspo roped a game-tying single to center, setting the stage for Reddick's heroics.
"That's one of the best characteristics of this team," Lowrie said. "We had that last year and we're off to a good start this year of really grinding out those last inning at-bats and making it tough on the other guys, never making it easy on them."
Qualls said his sinker was flat, and it was telling. After posting a 77.7-percent ground-ball rate -- the best of his career -- last season with the Marlins, none of the four balls the A's hit in the ninth inning Saturday were on the ground.
"I don't know if I was trying to generate more power," Qualls said. "I haven't been out in a while and everything else had been going on this week. My sinker had been flat, and looking back on it, I didn't get any ground balls, which is super uncharacteristic of myself.
"Obviously, I'll get it locked in and get it back to the way I was throwing. I felt I was in such a groove there. I got bitten by the sickness everybody was getting. That's definitely not an excuse. We've got to go out there no matter what and get the job down."
Oberholtzer, who was sent home from the ballpark on Friday because he wasn't feeling well, pitched well enough to win once again. He worked around eight hits in 5 2/3 innings, but still hasn't won in four starts this season despite a 3.04 ERA.
He has pitched at least five innings in his first 13 Major League starts, which ties a franchise record.
"I knew I had to come in and suck it up for the team and make some quality pitches and try to go as deep as I can in the ballgame and give the team an opportunity to win," he said.
The bullpen recorded some big outs in support of Oberholtzer. Bass got Lowrie to pop out with the bases loaded and end the sixth, and Albers pitched out of a jam in the eighth. Astros relievers have a 5.34 ERA this season and have allowed seven runs in 10 1/3 innings in two games against the A's.
"We're going to continue to go with the guys that are down there," Porter said. "That's all we can do. We can't go with somebody who's not down there. The guys down there are going to have to get it done."
Jonathan Villar paced the Astros offensively with a solo homer in the third inning -- his third of the season -- and a fifth-inning double, which led to an unearned run. Villar also made a terrific defensive play in the hole at shortstop in the second, backhanding a ball off the bat of Nick Punto and throwing him out.
Houston native Scott Kazmir pitched eight innings for the A's, allowing six hits and three runs in a no-decision.
"I thought he pitched great again," Oakland manager Bob Melvin said. "At times we didn't play great behind him. And we'll continue to work on it. He doesn't let that stuff bother him. Threw over a 100 pitches today basically in the same fashion we've seen him every time. He certainly didn't deserve to get a loss."