Ciguatera is caused by consuming reef fishes containing toxins produced by epiphytic dinoflagellates in the genus Gambierdiscus. Climate change and overfishing alter reefscapes, potentially increasing Gambierdiscus spp. habitat availability or altering how ciguatoxins (CTX) move through food webs. It is not clear how altered reefscapes influence the prevalence of ciguatoxic fishes posing a health risk to communities dependent coral reef fisheries. Therefore, the objectives of this study are to evaluate the relationship between a habitat and environmental characteristics at multiple spatial scales on the probability of fish testing positive for CTX and the concentration of CTX using a semi-quantitative in vitro neuro-2a cytotoxicity assay on two common species: Roi (Peacock Grouper) Cephalopholis argus and Kole (Goldring Bristletooth) Ctenochaetus strigosus sampled bi-annually across four sites along west Hawai'i Island. Both the probability of Roi testing positive and CTX concentration in Roi increased with fish length and decreased with the exposure to periods of high temperatures and fishing pressure. For Kole, the probability of testing positive for CTX and CTX concentration decreased with fish length, exposure to high temperature periods, effluent, fishing pressure. At small spatial scales, climate change and fishing pressure seem to be influencing the prevalence of ciguatoxic fishes, though not always in the ways expected. While most fishers likely take the risk of ciguatera in stride and have beliefs and practices to mitigate risk, these results suggest that those practices may lose effectiveness under altered conditions and necessitate better communication between researchers, managers, and stakeholders to adapt.