Gary Sanchez capped a four-run first inning with a three-run homer and Fernando Tatis Jr. added a solo shot an inning later as the San Diego Padres defeated the visiting Cleveland Guardians 6-3 on Tuesday night in the opener of a three-game interleague series.

Padres right-hander Joe Musgrove held the Guardians to three runs on seven hits and a walk with five strikeouts over six innings to earn the win and improve to 4-2. Josh Hader picked up his 16th save with a scoreless ninth.

Cleveland starter Tanner Bibee (2-2) immediately put himself in trouble by walking the first two hitters he faced -- Tatis and Juan Soto. Tatis moved to third on Manny Machado's flyout to right and scored on Xander Bogaerts' sacrifice fly.

After Jake Cronenworth singled, Sanchez lined the first pitch he saw from Bibee 396 feet to left-center for his sixth homer in 13 games as a Padre to make it 4-0.

Cleveland scored single runs in the second and fifth. The Padres countered with a run in the bottom of each inning.

Josh Bell, who spent the end of last season with the Padres, homered off Musgrove to lead off the second. His 346-foot drive to right came on an 0-2 slider. It was Bell's sixth homer of the season.

Tatis' 13th homer of the year came in the bottom of the second on an 0-1 curveball from Bibee and traveled 405 feet to center.

Will Brennan singled off first baseman Cronenworth's glove to open the fifth, moved to third when Cam Gallagher lined a double past Machado and scored on Steven Kwan's one-out groundout to second.

Machado opened the Padres fifth with a single, moved to second on a wild pitch and scored on a Bogaerts double that ended the night for Bibee, who gave up six runs on eight hits in four-plus innings. He walked two and struck out three.

Jose Ramirez singled to open the Cleveland sixth, advanced to third on a single by Josh Naylor and a forceout and scored on Tyler Freeman's sacrifice fly to left.

--Field Level Media