Top seed Ferrer led his quarter-final with Kevin Anderson on Thursday after taking the first set 6-2 before a strain on his left leg meant he had to retire at 4-2 down in the second, much to his frustration.
Earlier this month, the 31-year-old Spaniard won the ATP Copa Claro title for a third year running and had hoped to build on that success in Acapulco.
However, the world number four now faces an anxious wait to see how long he will be sidelined for.
"I'm very sad because I was playing great," reflected Ferrer.
"I still do not know the extent of the injury."