CHICAGO -- The Cubs came into this series against the Cardinals knowing that things were not going to be easy. Chicago expected a St. Louis team ready to put up a fight, even without a group of regulars available and with its season schedule majorly disrupted.

"We can't write off anybody," Cubs starter Kyle Hendricks said this week. "We knew it was going to be a grind. Even though it's a 60-game season, it's still going to be a grind every single game, especially in our division."

The Cardinals reiterated that point by dealing the Cubs a 9-3 loss in the opener of a seven-inning doubleheader on Wednesday. That pulled the series even, 2-2, as part of a five-game, three-day marathon between the historic rivals before Chicago won the nightcap, 4-2.

• Box score

Here were three key aspects of the Cubs' loss.

1. First-inning setback
One of the strengths of the Cubs' rotation this season has been quieting the top of lineups. And, as a result, that has put Chicago's offense in a consistent position to grab an early lead.

The Cubs headed into Wednesday having outscored their opponents by 10 runs (12-2) in the first inning this season. That included a Major League-leading 0.82 ERA in the first inning by the North Siders' rotation. Chicago was riding a nine-game streak without allowing a run in the first frame, dating back to Aug. 6.

That streak came to an emphatic end in the first inning of Game 1.

Cubs righty Alec Mills began by hitting Kolten Wong with a pitch and then allowed a single to center to Tommy Edman. Paul Goldschmidt followed with a walk, prompting a mound visit from Cubs pitching coach Tommy Hottovy.

“It just looked like a command issue, for me," Cubs manager David Ross said. “Didn’t look like he had any command of his secondary stuff early on. I don’t know that he threw too many strikes with the secondary stuff, so he was having to battle, trying to pitch with the two- and the four-seam fastball.”

That brief chat did not do the trick, as Matt Carpenter then drilled a 2-1 sinker from Mills to center field, where it clanked off the empty bleacher seats for a grand slam. That quick strike by St. Louis' offense put the Cubs on their way to the loss column.

With a second game looming, Mills did what he could to salvage a useful start for the Cubs. The right-hander worked into the fourth, finishing with 86 pitches and six runs charged to his line.

“Once that happened, for me in my head it was, ‘Just go as long as you can,’” Mills said. “For me, I just try to do what I can to help the team. If it’s staying out there when you don’t have it and throw as many pitches as you can to save the bullpen, then that’s my job today.”

2. Leaving them loaded
Twice on Tuesday night, the Cubs loaded the bases -- only to come up empty in three plate appearances. Chicago's lineup had ample traffic all evening, though, and broke through enough times to overcome those misfires.

In Game 1 on Wednesday, the bases-loaded troubles cost the Cubs.

Chicago chased Cardinals ace Jack Flaherty in the second inning, when he issued two walks (Willson Contreras and Jason Kipnis) and hit a batter (Nico Hoerner) to fill the bags with two outs. That set things up for Ian Happ, who struck out swinging against lefty Austin Gomber.

One inning later, Gomber hit Kyle Schwarber and issued consecutive free passes to Contreras and Jason Heyward, loading the bases again for the Cubs. With two outs, Kipnis chopped into a 4-3 groundout to strand three baserunners again.

On the season, the Cubs have gone just 5-for-27 (.186) with 13 strikeouts, one walk and no extra-base hits with the bases loaded.

“I wouldn’t say it’s an approach thing,” Ross said. “It’s hard to hit in general. I think the more you put yourself in those situations, good things are going to happen. We continue to do that a lot. We’ve talked about just finding that ball that falls for us, or one that goes over the fence. That’s the important part is just get one to go our way.”

3. Happ stays hot
Flaherty fired a four-seamer above the strike zone in the first inning, and Happ still found a way to get the barrel on it. From there, the baseball went on a long ride -- over right field and off the videoboard behind the bleachers.

That marked Happ's third homer in his past four games, moving him into the team lead with six blasts this season.

"Coming into this, there was a couple 'X' factors for me,” Ross said. "Looking at some things, talking to my coaching staff, I knew Ian Happ was going to have to play a big role for us."

So far, Happ has not disappointed. The issue in Game 1 was that the Cubs then went 0-for-20 into the seventh, when Josh Phegley snapped that skid with a two-run homer, his first hit with the Cubs.

Happ now has a .314/.442/.657 slash line with a team-leading 14 RBIs through 23 games for Chicago. He has been one of the best hitters in the National League, and he is currently filling the leadoff spot in place of an injured Kris Bryant.

"Him playing well has definitely kind of solidified my thoughts this offseason," Ross said. "We knew he had that production in him, and he had the capability of doing that, but just going out and doing it is kind of what we needed to see."