Abstract Interactions between baculoviruses and insecticides vary from synergism to antagonism. The granulovirus infection of Spodoptera litura (SpltGV) produces slow kill of the tobacco cutworm larva. Hence, we tested SpltGV in combination with several insecticides including, endosulfan 35EC, chlorpyrifos 20EC, fenvalerate 20EC, and cartap hydrochloride 25WP for synergistic insecticidal activity. We found that interaction between virus at a lethal concentration for 25% mortality (LC25) dose and LC25 and LC50 dose of insecticides was synergistic with chlorphyriphos, additive with fenvalerate and endosulfan and antagonistic with cartap hydrochloride. A significant mitigation of the carboxyl esterase induction was observed for chlorpyrifos treatments applied 48 and 96 h following virus inoculation. Our results indicate that co-application of the granulovirus along with chlorpyrifos reduces the induction of carboxyl esterase. Application of the virus along with insecticide may be an effective insecticide resistance management strategy.