The protozoan Perkinsus marinus was identified for the first time in the oyster Crassostrea corteziensis from the state of Baja California Sur, Mexico. Intensities of P. marinus infections increased from 0.5–2 to 2–5 (Mackin scale) when water temperature was experimentally increased to 26°C for 15 days. Although disease-induced mortalities have not been reported in natural populations of C. corteziensis, high injected doses of P. marinus caused mortalities among experimental oysters. To evaluate the response of C. corteziensis with increasing levels of P. marinus, expression levels were investigated for genes involved in phagocytosis, cellular proliferation, apoptosis, and inhibitors of serine proteases. Oysters with low infection showed higher gene expression of the serine protease inhibitor gene, as well as of genes involved in phagocytosis (nicotinamide adenine dinucleotide phosphate-oxidase, actin, superoxide dismutase, and glutathione s-transferase), and genes involved in apoptosis and DNA fragmentation (tumor necrosis factor and caspase-8). Results of observed mortalities associated with high intensities of P. marinus infection indicated that C. corteziensis is a susceptible host to this pathogen. Phagocytosis and cell death by apoptosis were higher in less-infected oysters, as an apparent result of the increased expression of apoptosis-related genes.