Oxford United were left counting the cost of their first defeat under new boss Darren Patterson at Victoria Stadium on Saturday.
Alex Jeannin was sent off, along with Northwich defender Richard Battersby, but of greater concern was that the U's lost striker Matt Green and midfielder Eddie Anaclet to serious shoulder injuries.
Green broke his collarbone in only the second minute while Anaclet dislocated his shoulder after Battersby slid in dangerously near the touchline midway through the second half.
Many U's players were angered by Battersby's challenge, and Jeannin and the Northwich player squared up to each other, head to head.
Referee Chris Harwood showed both players the yellow card, and both had been booked earlier - so both were ordered off down the tunnel.
This Blue Square Premier game was played in very difficult conditions, with heavy rain making the pitch greasy and injuries likely.
To wrap up a very disappointing day for Oxford, it was their former striker Lee Steele - whose goal had condemned them to relegation from the Football League two seasons ago - who netted the winner for Northwich eight minutes before half-time.
United suffered the early blow of losing Green inside two minutes. He did it in a seemingly innocuous challenge with the Northwich keeper, and he was replaced immediately by Yemi Odubade.
Playing for a change in an all-blue away strip, the U's had an unfamiliar look about them with Matt Day in central midfield alongside Eddie Hutchinson, but otherwise there were few changes to the side which had drawn 0-0 with Southend in the Cup.
Despite hours of rain, which continued through the game, the pitch held up remarkably well, a tribute to the drainage at Victoria Stadium. So although many of the local fields were flooded, there was no surface water on the pitch itself when the game kicked off.
But as the afternoon wore on, and the rain continued to lash down, it became more slippery by the minute.
Eddie Anaclet showed his confidence with a first-time control of the ball with his fright foot and then left-foot shot from just inside the area, but keeper Scott Tynan got behind it.
And it was Anaclet again on the end of a good chance on 16 minutes, but his side-footed effort from eight yards was turned around his post by the foot of Tynan.
The Vics' big centre forward, Lucas Akins, was a handful and the home side managed to get some decent crosses to him, Luke Foster having to be at his best to deal with his opponent.
Day tried his luck with a long-range shot from nearly 30 yards, with his lleft foot, but Tynan got down on his knees to save.
Certainly, in the conditions, it was worth trying to shoot whenever possible.
Right back James Clarke was sometimes allowing left winger Luke Horrocks too much space to get in crosses, but the teenager produced a great piece of defending to shoulder-barge Horrocks off the ball and then backheel to teammate Anaclet.
But in the 37th minute, Northwich took the lead with a well-worked goal from Steele, who received the ball into his feet from Akins, swivelled and shot low past Billy Turley.
United had a great chance to equalise, though, two minutes into the second half when Ashley Barnes' flicked on Alex Jeannin's long free-kick to set Yemi Odubade free on a run on goal. It was a good first touch from Odubade, but Tynan managed to deflect his shot and Anaclet was unable to turn in the rebound.
Patterson sent on Joel Ledgister for Barnes soon after and switched things around, putting Gary Twigg up front alongside Odubade, with Anaclet coming to left midfield.
The visitors had good possession in the second half, but created few clear openings.
After the two red cards, which came with 20 minutes to go, and Anaclet's injury - he went off down the tunnel in great pain - the U's boss sent on Michael Corcoran to fill the void.
Oxford Utd: Turley; Clarke, Quinn, Foster, Jeannin; Anaclet (Corcoran 73), Hutchinson, Day, Twigg; Green (Odubade 3), Barnes (Ledgister 56). Subs not used: Worrall, Posey.
Att: 911.
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