Keothavong won the first set but could not maintain her momentum
Anne Keothavong's campaign at her first tournament back after injury came to an end in the quarter-finals of the Dow Corning Classic in Midland, USA.
After two victories in the ITF event, the 26-year-old went down 4-6 7-5 6-3 to Poland's Marta Domachowska despite twice getting to match point.
There was better news for British number one Elena Baltacha, who beat Rebecca Marino 6-4 6-4.
The Scot will take on Domachowska for a place in the final.
Keothavong, who injured her knee last July, returned to action in the Fed Cup earlier this month.
"It's disappointing to lose a match like today after having two match points but I'm pleased overall as I'm back competing again and this is just the start of my comeback," the Londoner told BBC Sport.
"I had the match there for the taking and just lost a bit of focus, in the third set I was struggling physically and could barely move in the last few games.
"I've played more matches than I expected in the last two weeks and it's taking a toll on my body, but hopefully I'll recover in time for Memphis."
Next week Keothavong moves on to Memphis, where she reached the semi-finals last year, and she will face Germany's Kristina Barrois in the first round.