CINCINNATI -- Based on the numbers coming in, an extended battle of the bullpens against the Padres was not a favorable situation for the Reds to have. San Diego came into Tuesday with the best bullpen ERA in baseball (2.85) while Cincinnati entered with the worst (5.49).

The Reds’ bullpen walked a tightrope often but largely held its own most of the night. Their offense spent the evening playing catch-up but came up short in a 5-4 loss to the Padres at Great American Ball Park. Four of their five losses to San Diego this season have been by two runs or fewer.

• Box score

"I feel like we’ve been so close to turning the corner as the bullpen as a whole here lately," said Reds reliever Brad Brach, who pitched a scoreless eighth inning. "Really, just to keep us in the game there, just put up zeros and give our offense a chance is really all you can ask for."

In the last six games -- against three opponents -- the Reds’ bullpen has a 1.80 ERA.

San Diego has won 10 of its past 11 games, starting with its four-game sweep of the Reds at Petco Park two weeks ago. Four of the Reds' five losses against the Padres have been by two runs or fewer.

"Man, we gave it a shot and so many little things could have gone different to make it a different game," Reds manager David Bell said. "Our bullpen, what a great job they did to give us the opportunity, and a ball falls in here or there and it would've been a great game to win. It's a good team we're playing."

The Padres had to lean on their relievers from the get-go after scheduled starter Blake Snell was scratched with an illness. On the other side, Reds starter Tony Santillan muddled through three innings while throwing 75 pitches and allowing three runs (two earned), six hits and two walks with four strikeouts. Twice, Santillan escaped with the bases loaded.

"He was just missing with pitches, and that was kind of the difference," Bell said. "It led to his pitch count getting up a little bit too high there in the third."

This could likely be Santillan's last start in the big leagues for a while, with Sonny Gray due to return from the injured list on Friday. The club will weigh whether to move Santillan to the bullpen as a long reliever or have him keep starting at Triple-A Louisville.

After Santillan departed trailing by a 3-1 score, rookie Ryan Hendrix opened the fourth inning by giving up Tommy Pham's leadoff homer to right-center field. With one out, Hendrix hit Jake Cronenworth with a pitch and allowed a Manny Machado single. After lefty Josh Osich took over, Trent Grisham hit an RBI single before Osich got out of the inning with a double play. Those were the only runs the bullpen allowed over six innings.

Cincinnati rallied with three hits in the fourth inning against lefty Nick Ramirez. One run scored when Shogo Akiyama hit an RBI single that brought Joey Votto home just ahead of a tag at the plate.

In the fifth inning against Nabil Crismatt, Jesse Winker made it a one-run game with a two-run homer to right-center field -- his team-high 19th of the season. But it was as close as the Reds could get as the Padres allowed just one infield hit and a walk the rest of the way.

"I feel like every time we play these guys it’s a really, really good game, it’s a dogfight," Winker said. "Everybody that pitched tonight really pitched well. That’s a tough lineup over there, and they can really hit, so keeping them to five was really big. It was just a really good game. Obviously, it was unfortunate we didn’t come out with the win."

San Diego kept threatening to add on but failed. After Art Warren pitched a 1-2-3 fifth, he returned for a rare multiple-inning outing in the sixth. Warren gave up a hit and a walk before picking up two outs. Amir Garrett took over and walked his first batter, Grisham, but got Eric Hosmer to look at strike three to leave the bases loaded.

Sean Doolittle also left the bases loaded during a scoreless seventh inning. A runner was left in scoring position by Brach in the eighth, which ended with him striking out Wil Myers after a 12-pitch duel. Heath Hembree issued a pair of two-out walks in the ninth but escaped as well.

Overall, the Padres left 16 men on base -- their most in a nine-inning game since the 1985 season.

"We’re here to win baseball games. That’s what we get paid to do," Brach said. "It’s great that we played a tight game and that we had a shot to win, but at the end of the day, we’re here to win games. Those are the kind of games you have to win to get into the playoffs and games you have to win when you’re in the playoffs. That’s a playoff-caliber team over there, obviously. It’s just frustrating to come up so close every time I feel like we’ve played them so far."