Yangervis Solarte and Matt Kemp each had two hits and drove in a run for San Diego, which has won seven of eight and 12 of 16. Craig Kimbrel, who allowed a tying solo homer in Friday's 8-3 win that sent the game to extra innings, pitched a perfect ninth for his 31st save in 33 chances.
Despaigne (5-7) allowed two runs and five hits in his second straight win against Miami. He also pitched six solid innings in a 3-2 victory over the Marlins last Sunday.
San Diego grabbed control with four runs in the third inning against Jose Urena (1-5), extending its lead to 5-0. Solarte hit an RBI triple and scored on Kemp's sacrifice fly. Derek Norris' double and an error by left fielder Derek Dietrich brought home two more runs.
The Marlins cut the deficit to 5-2 in the fifth on back-to-back RBI singles by Donovan Solano and Dee Gordon.
Justin Bour had a run-scoring fielder's choice for Miami in the seventh, but Joaquin Benoit retired all three batters he faced in the eighth before Kimbrel finished.
Padres: RHP Brandon Morrow (shoulder inflammation) had another setback when he felt discomfort during his latest bullpen session. ... C Tim Federowicz (right knee) was activated from the 60-day disabled list and was designated for assignment. ... 2B Cory Spangenberg (bruised left knee) is expected to begin a rehab assignment next week.
Marlins: All-Star RF Giancarlo Stanton (left wrist) is still working his way back after having surgery on June 28, and the process has gone slower than expected. "Definitely slower," Stanton said. "That's the generation of your whole swing is that turnover (with) your hand and your wrist. I know what a sore wrist feels like and now with a broken hand and the sore wrist, it takes a little longer." There is no timetable for his return following the original diagnosis of being sidelined for four to six weeks.
Padres: RHP James Shields (8-4, 3.77 ERA) is 1-4 with a 4.01 ERA in his last 10 starts, but has been much better over his last three with a 1-1 mark and 2.12 ERA.
Marlins: RHP Jose Fernandez (4-0, 2.53 ERA) is looking to improve to 16-0 at home in his career with Miami when he takes the mound Sunday. Fernandez has a 1.17 ERA in 22 career home starts, which is the lowest through a pitcher's first 22 home starts since 1920.