Celtic suffered their fifth consecutive defeat in the Women's Champions League as Signe Bruun's double set up victory for Real Madrid.
With progression in the competition not possible, Elena Sadiku's side were playing for pride and history, in search of their first ever group-stage point.
For large parts of the first half in freezing and foggy conditions, there was confidence the priceless point could be picked up for Celtic in their final home game in Hamilton, but their hopes were dented with a class strike.
Norway international Bruun, who headed in Real Madrid's third in their reverse win, was allowed too much time to tee up a thunderous shot from outside the box to beat Kelsey Daugherty.
The Celtic goalkeeper had been beaten seconds before by Caroline Weir, but the Scotland international was denied a goal in her homeland by the offside flag.
The 29-year-old tried with all her might, but was unable to find a legitimate goal on a dominant night for Real, who had already secured qualification to the knockout phase.
Their dominance deserved to be reflected in the scoreline, and Bruun's bullet header from three yards out provided the comfort their play merited, before Alba Redondo nodded home to round off the scoring.
Pre-match, head coach Sadiku said she believed Celtic "deserved" something to show for their efforts so far, and while they added passages of positive play and creativity to that cause, they struggled to step up to the next level again.
Celtic close out their maiden group-stage campaign away to Twente on Tuesday, while Real Madrid host Chelsea, who top Group B with five wins from five.