The pervasive use of organophosphorus compounds as pesticides in recent years has posed a major threat to the population especially to the occupational workers. Once developed as a chemical warfare in the early 1940’s and having been used in World War II as nerve toxic agent, it has gained entry to almost every household worldwide. Malathion, the OP insecticide was first registered for use in 1956 in the United States. The deleterious effects of Malathion are less studied and have been intriguing to the researchers. The current study focused on the immunosuppressing effect of Commercial Grade Malathion (CGM) on normal and infection induced mice assayed by three immunological markers the Adenosine Deaminase (ADA) levels, Hemagglutination titer (HA) and Carbon Clearance index (CCI). A comparative study was made on normal and subcutaneous Staphylococcus aureus (SA) infected mice exposed to 5% LD50 of CGM. The results obtained showed adverse effect on immunological response in mice that were exposed to CGM alone and in mice exposed to CGM plus subcutaneous S. aureus infection. The effect of CGM was observed by an increase in ADA, decrease in antibody-producing capacity in HA assay and decrease in carbon clearance capacity being greater in the CGM plus subcutaneous SA infection group. This indicates that immunosuppression by pesticide chemicals may be greater in different pathological conditions like an infection in which the immune status is compromised.