Abstract: Until now, knowledge about bivalve mollusk diseases in tropical waters of Asia is scarce. A histopathologic survey was performed on the slipper-cupped oyster, Crassostrea iredalei from the Malaysian waters for the first time to investigate the presence of parasites and their effects on host tissues. C. iredalei samples were collected from Pulau Betong, west coast of Penang, Malaysia. A total of 60 oysters were examined from October 2010 to January 2011. After shell height measurement, the samples were dissected. A transverse section (3 mm) was cut through the anterior part of the soft body containing gills, mantle, digestive glands, gonads and foot tissue. The sections were processed by standard histological techniques, stained with hematoxylene and eosin and examined under microscope. A protozoan parasite, Nematopsis sp. was detected from the connective tissue of digestive gland tubules, gills, mantle and gonads. The prevalence of infection of Nemaptosis sp. were 15% each during October and November and 30% during January. The maximum number of hemocytes containing Nematopsis sp. per histological section was 5. The oocysts were oval in shape and maximum no. of oocysts per hemocyte was 7. No pathological threat was detected from the histopathological survey performed. This preliminary survey will be useful for planning a health monitoring programme for the natural and cultivated slipper-cupped oyster and other bivalves of commercial importance in Malaysian waters.