Jamie Murray and partner Bruno Soares were beaten 4-6 6-0 10-6 by French pair Pierre-Hugues Herbert and Nicolas Mahut in the Monte Carlo Masters final.
The Australian Open champions won the opening set but were blown away in the second before losing the first-to-10 match tie-break that decided matters.
Murray remains top of the ATP doubles rankings after his semi-final win.
Eight-time champion Rafael Nadal plays Frenchman Gael Monfils in the singles final at 13:30 BST.
Murray was taking part in his first Masters 1000 final but could not have asked for tougher opponents with the French third seeds on a 12-game winning streak and having won the last two Masters finals.
Promising start fizzles out
The start was delayed half-an-hour because of rain and it was Murray and Soares who adjusted best to conditions before breaking the Mahut serve in the eighth game.
Murray served for the set but a double fault allowed the French pair to break back, only for Murray and Soares to again break serve after winning a thrilling exchange of reflex volleys at the net.
Despite being overlooked by France's Davis Cup captain Yannick Noah, Herbert and Mahut are top of the current order of merit and it was no surprise when they came storming back in the second set.
They broke Murray twice more and Soares for the first time to take it without dropping a game in just 25 minutes.
The French continued their dominance in the match tie-break and opened up a 5-1 lead, but Murray and Soares rallied to get it back to 7-6 only to let it slip out their grasp again with Murray serving a double fault at match point.
A gracious Murray told the crowd: "They were on fire and too good for us today. I hope Yannick Noah is watching."