Xenorhabdus nematophila and Photorhabdus luminescens are entomopathogenic bacteria that have mutualistic relationships with their respective nematode hosts, Steinernema carpocapsae Weiser (Rhabditid: Steinernematidae) and Heterorhabditis bacteriophora Poinar (Rhabditidae: Heterorhabditidae). These symbiotic bacteria are delivered into insect hemocoel by nematodes and rapidly activate the immune system of their target species. We show here that both these bacteria influence cellular and humoral defenses in fifth instar larvae of Spodoptera exigua Hübner (Lepidoptera: Noctuidae). Larvae treated with both bacterial species possessed a higher number of hemocytes than either negative controls at initial hour post-injection (hpi) although both the frequency of hemocytes and granulocytes decreased. Results show that at times between 12 and 16 hpi the densities of both fell below the level of the negative control. The hemocyte population also fell below that seen in the negative control in larvae containing heat-killed bacteria, while nodule formation was observed in cases of both live and heat-killed bacterial treatments. We also show that the abilities of live symbiotic bacteria to influence a decrease in nodule formation were higher than was the case for their heat-killed counterparts and that no nodules formed during negative control treatment. Data show that both live and heat-killed symbiotic bacteria initially activated a range of insect defensive enzymes (including protease, phospholipase A₂ [PLA₂], and phenoloxidase [PO]) post-injection compared with the negative control but that their activation levels fluctuated in different ways. The results of this analysis show that attacin, cecropin, and spodoptericin were upregulated by the injection of live symbiotic bacteria; the expression levels of these proteins were higher than in both normal larvae (noninjected) and negative control treatments. We show that attacin and cecropin expression rates due to live P. luminescens treatments were less than was the case for live X. nematophila treatment while the expression of spodoptericin was reversed. Results indicate that the ability of P. luminescens to suppress cellular reactions, including the expression of attacin and cecropin, is higher than is the case for X. nematophila. The results of this study provide new insights into the roles of P. luminescens and X. nematophila in countering insect physiological defenses.