Barnsley were knocked out of this year's Emirates FA Cup at the last 16 stage by Premier League giants Chelsea.
Having already been eliminated from the Carabao Cup by the Blues earlier this season, the Reds were dealt a repeat blow here at a bitterly cold Oakwell.
Tammy Abraham's second half finish from close-range was enough for Thomas Tuchel's in-form side, who barely threatened the Reds otherwise in a game the hosts dominated in terms of chances.
Reds' Head Coach, Valérien Ismaël had spoken in the build-up about his team needing to put in a top performance and to be clinical when chances arose. Unfortunately, the performance was there but again against quality opposition, the Reds froze in front of goal.
Wing-back Callum Brittain had two golden opportunities in the opening 45, first when latching onto Alex Mowatt's cross via a Conor Chaplin flick-on, but his effort from a couple of yards out found Blues 'keeper Kepa when it looked easier to score.
The same player was out of luck from a short corner when after finding room inside the box to shoot, his goalbound effort came off teammate Victor Adeboyejo and trickled just wide of the Chelsea goal.
Toby Sibbick put in a last-ditch tackle to thwart Abraham inside the box, which was the visitors best attacking move of the first half, with the Blues claiming a penalty, turned down by referee Martin Atkinson.
HALF-TIME: Reds 0-0 Chelsea
The away side reshuffled a little during the break, moving to a 4-3-3 system and making a couple of changes, and whilst this enabled them to see more of the ball, it was still the Reds asking all the questions, as Chaplin dragged wide from the edge of the box.
There was a warning on the hour-mark when Sibbick was beaten by the dangerous Callum Hudson-Odoi out wide, but the England man fired his low effort just wide of the far post.
Latest signing, Daryl Dike made his first Reds appearance, along with introductions for all of Jordan Williams, Romal Palmer, Dominik Frieser and Michael Sollbauer as Ismaël looked for fresh legs to make an impact.
But it was the West Londoners who struck the fatal blow on 64 minutes when just seconds after Antonio Rudiger had powered a header a yard wide, Abraham escaped his marker inside the six yard box to convert a Reece James cross, with Reds players stunned when the offside flag wasn't raised. It looked very close from the press box.
But the Reds fought on regardless and there was a wonderful chance in the final 10 minutes when Sollbauer hooked an ambitious effort that was heading into the net only for that man Abraham to clear off the line with his head, right under the crossbar!
It had been a heroic display by the Reds, but without reward. It's back down to league business for the rest of the 20/21 campaign.
FULL-TIME: Reds 0-1 Chelsea
Collins, Brittain (J.Williams), Sibbick (Sollbauer), Helik, Andersen, Styles, Mowatt, Kane (Palmer), Chaplin (Frieser), Woodrow, Adeboyejo (Dike).
Unused: Walton, Oduor, Moon, Thompson.