Two first half goals from Barnsley ended Boro’s interest in the Carabao Cup at the second round stage.
Boss Neil Warnock watched the game from one of the West Stand boxes after feeling unwell upon arrival, and he watched on as a much-changed team from last weekend’s opener against Watford suffered a first home defeat of the season.
Boro, giving a debut to new recruit Sam Morsy, had started brightly enough. Marcus Browne headed wide from a Marc Bola cross and Lewis Wing warmed the hands of Brad Collins with a strike from distance, but Barnsley soon settled.
The visitors opened the scoring midway through the first half when Patrick Schmidt was on hand to finish off, drilling the ball home, after Barnsley played the ball across the edge of area.
And it was 2-0 before the half-hour when Jordan Williams played a neat one-two to find space deep inside the area and he converted from a tight angle.
Boro introduced Paddy McNair at half-time and also introduced Jonny Howson and debutant Sam Folarin during the second period, in the hope of forcing a way back into the game.
Marcus Tavernier forced Collins into making a second half save, while Wing drilled an effort wide as the game entered the final quarter.
Collins also had to be alert tip a Paddy McNair free-kick over the top as Boro piled forward in search of a route back into the game. Folarin went close when he headed wide, but there was to be no way back into the contest.