Insect pericardial cells (PCs) are strategically located along the dorsal vessel where they encounter a high hemolymph flow enabling them to undertake their osmoregulatory, detoxifying, and scavenging functions. In this location, PCs also encounter foreign molecules and microorganisms. The response of PCs of the mosquito Anopheles albimanus, one of the most important Plasmodium vivax vectors in Mexico and Latin America, to Saccharomyces cerevisiae was analyzed by using biochemical, cellular, ultrastructural, and bioinformatics approaches. Immune gene transcripts were identified in the PC transcriptome of A. albimanus. PCs responded to the presence of yeast and zymosan with increased lysosomal and phosphatase activities and produced lytic activity against bacteria. Our results indicate that mosquito PCs play a key role in the neutralization and elimination of pathogens.