Anne Keothavong was unable to build on a good start against Mirjana Lucic as she was sent tumbling out of the Strasbourg International at the first-round stage.
Keothavong won the first set against the former Wimbledon semi-finalist, who is now ranked 119 in the world - 43 places lower than the British number two, but the Croatian battled back to take the victory 2-6 7-5 6-4.
In losing, Keothavong joined fellow Briton Elena Baltacha in making an early exit from the claycourt tournament. Baltacha suffered a straight-sets defeat to Stephanie Foretz Gacon on Monday.
Both players will now head to Paris for the French Open which begins on Sunday. Both have direct entry into the main draw at Roland Garros.
In other action on Tuesday, third seed Maria Kirilenko was forced to retire injured midway through her match against American Sloane Stephens.
The Russian took the first set 6-3 but lost the second 7-5 before she was forced to withdraw with a right ankle problem, denying the tournament another leading name following top seed Sabine Lisicki's shock exit to Pauline Parmentier on Monday.
But there were no such problems for second seed Francesca Schiavone, who continued her build-up towards a shot at a second French Open title by beating Romania's Alexandra Cadantu 6-1 6-2. Fourth seed Anabel Medina Garrigues also won.
However, three more seeds followed Kirilenko out, with fifth seed Mona Barthel falling 6-4 7-6 (9/7) to Russian qualifier Alexandra Panova, and sixth seed Marina Erakovic and ninth seed Aleksandra Wozniak losing to Ayumi Morita and Shahar Peer respectively.
There were also victories for Lucie Hradecka, Alize Cornet, Virginie Razzano, Timea Babos and Johanna Larsson.