ANAHEIM -- One of the Angels’ biggest issues this season has been sloppy plays on defense leading to big innings. That haunted them once more against the Astros on Wednesday.

After right-hander Griffin Canning cruised through the first three innings, he was hurt by several defensive miscues in a four-run fourth to hand the Angels a 5-4 loss in the series finale at Angel Stadium. Giving up big innings has become a recurring theme for the Angels, as they’ve allowed at least three runs in a frame in each of their last five games, going 1-4 over that span.

​​“It’s really been that one-inning bugaboo for us,” said manager Phil Nevin. “We made a couple mistakes in those innings, so we’re working to clean it up and get better. I think our defense has played well and I think we pitched well enough to win more games this homestand than we did.”

Canning’s lone blemish through three innings was a solo homer to Yordan Alvarez on a 97 mph fastball above the zone in the first. He was handed a one-run lead with Hunter Renfroe connecting on a two-run homer in the second for his team-leading 10th blast of the year.

But it unraveled in the fourth after Kyle Tucker singled with one out. Corey Julks followed with a slow roller off the end of his bat, but it went under third baseman Anthony Rendon’s glove and past shortstop Zach Neto into left field. It was ruled a tough-luck single and allowed Tucker to go to third.

“It’s a do-or-die play for Tony,” Nevin said. “It's tough to sit here and say Neto should've backed him up, because he was probably going to third in case it does get by him to the outfield. It's just a tough play and it stayed down on him. It's not an error, it's a tough play. But it's a play Tony would say he'd want to make."

Yainer Diaz followed with a sacrifice fly to left field to tie the game before Canning made a throwing error on a pickoff to first base. It allowed Julks to reach third and was the club’s 28th error on the season, which is tied with the Giants for the most in the Majors. Canning then walked David Hensley on five pitches to put runners at the corners.

The walk proved costly and the Angels were hurt by more bad luck with Jake Meyers reaching on an infield single on a slow roller to Rendon to bring home another run. Meyers was initially ruled out, but after a review, the call was quickly overturned.

Four pitches later, Canning hit Martín Maldonado with a fastball to end his outing after 3 2/3 innings and 64 pitches. Right-hander Jimmy Herget came in and promptly gave up a two-run single to Jeremy Peña, with both runs being charged to Canning. Herget walked Alex Bregman to load the bases but got Alvarez to fly out to left to get out of the jam.

“It was the third time through, and where Griff was, we have the day off tomorrow and a healthy bullpen, and they had two right-handers Jimmy had done well against in the past,” Nevin said. “The 0-2 pitch that was four or five inches off the plate, Peña just does a great job of sticking his bat out to get the ball to right field.”

Canning was charged with five runs on five hits and a walk to fall to 2-1 with a 6.38 ERA in five starts this year. He’s allowed five runs in back-to-back outings after surrendering three runs or fewer in each of his first three starts.

“Just baseball happened,” Canning said. “They put some balls in play that were tough plays and things happened. As [bad] as it feels, I still feel like I’m getting better every outing.”

That big inning loomed large in the ninth, when Shohei Ohtani connected on a two-run homer off closer Ryan Pressly to make it a one-run game. Rendon and Renfroe followed with singles but Brandon Drury, Matt Thaiss and Gio Urshela failed to plate the tying run.

Nevin liked the fight he saw at the end of the game and was still happy with the Angels’ efforts against Texas and Houston despite going 2-4.

“I feel like we can compete with anybody if those are the two best,” Nevin said. “The two games got away from us with Texas, but really, these last two games, we've had our chances.”