Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish-poisoning (DSP) toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the non-specific immune responses of bay scallop, Argopecten irradians. Various immunological parameters (superoxide dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (ALP), lysozyme activities, and total protein level) were assessed in the hemolymph of bay scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations (50, 100, and 500 nM) of OA. Moreover, the expression of immune system-related genes (MnSOD, PrxV, PGRP, and BD) was also measured. Results showed that SOD and ACP activities were decreased between 12 and 48 hpe. The ALP, lysozyme activities, and total protein levels were also modulated after exposure to different concentrations of OA. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that the exposure to OA had negative effects on the antioxidant and non-specific immune responses, and even disrupted the metabolism of bay scallops, making them more vulnerable to environmental stress-inducing agents; they provide a better understanding of the response status of bivalves against DSP toxins.