Knowles and Bhupathi were coming off a very exhausting second round match against Johan Brunstrom (SWE) and Jean-Julien Rojer (AHO) that may have taken a little too much out of them. The second round scores that saw a number of tie breaks were 7-5, 6(4)-7(7) and 7(7)-6(3).
The fourth seeded pair easily defeated Josselin Ouanna and Jo-Wilfried Tsonga from France in the first round in straight sets 6-3 and 6-2.
In their third round match there were signs of fatigue late in the match as Knowles and Bhupathi suffered three double faults compared to just one for their opponents.
The match was close throughout. Knowles and Bhupathi secured six aces compared to four for Acasuso and Gonzalez, but their low winning percentage on first serve of just 68 percent was also a tell tail sign that they were not playing at their optimum level. Acasuso and Gonzalez won 75 percent of their first serves.
Meanwhile, Knowles and Bhupathi also hurt their chances to win the match when they failed to convert on two of their three break point chances. Their opponents took advantage of two of the three break points they faced.
Knowles and Bhupathi will try to recuperate before playing in their next major event. They were coming off a second round loss at the Madrid Masters after having a bye in the first round of that tournament. Also in May the pair lost in the semi-final of the Italian Masters to Daniel Nestor and Nenad Zimonjic.