The xenoestrogen 4-nonylphenol (NP) is a ubiquitous aquatic pollutant and has been shown to impair reproduction, development, growth and, more recently, immune function in marine invertebrates. We investigated the effects of short-term (7 d) exposure to low (2 μg l−1) and high (100 μg l−1) levels of NP on cellular and humoral elements of the innate immune response of Crassostrea gigas to a bacterial challenge. To this end, we measured 1) total hemocyte counts (THC), 2) relative transcript abundance of ten immune-related genes (defh1, defh2, bigdef1, bigdef2, bpi, lysozyme-1, galectin, C-type lectin 2, timp, and transglutaminase) in the hemocytes, gill and mantle, and 3) hemolymph plasma lysozyme activity, following experimental Vibrio campbellii infection. Both low and high levels of NP were found to repress a bacteria-induced increase in THC observed in the control oysters. While several genes were differentially expressed following bacterial introduction (bigdef2, bpi, lysozyme-1, timp, transglutaminase), only two genes (bpi in the hemocytes, transglutaminase in the mantle) exhibited a different bacteria-induced expression profile following NP exposure, relative to the control oysters. Independently of infection-status, exposure to NP also altered mRNA transcript abundance of several genes (bpi, galectin, C-type lectin 2) in naïve, saline-injected oysters. Finally, plasma lysozyme activity levels were significantly higher in low dose NP-treated oysters (both naïve and bacteria challenged) relative to control oysters. Combined, these results suggest that exposure to ecologically-relevant (low) and extreme (high) levels of NP can alter both cellular and humoral elements of the innate immune response in C. gigas, an aquaculture species of global economic importance.