The increasing presence of antimicrobial agents and pesticides in aquatic environments raises concerns about their potential impacts on non-target organisms. Among these chemicals, deltamethrin (DM), a widely used pesticide, and sulfamethoxazole (SMX), an antimicrobial commonly detected in water bodies, pose significant ecological risks. This study investigates the acute toxicity, neurotoxic effects, oxidative stress responses, immune-related gene expression, and feeding behavior of adult zebrafish exposed to DM and SMX. The 96 h LC50 for DM was 4.84 mu g/L, indicating significant acute toxicity, while the LC50 for the DM + SMX mixture was 11.32 mu g/L, suggesting that SMX may mitigate the toxicity of DM. Neurotransmitter alterations, including reduced levels of gamma-aminobutyric acid (gamma-GABA), serotonin (5-HT), and acetylcholinesterase (AChE), were observed, with the combination of DM and SMX showing partial restoration of AChE activity. Oxidative stress markers revealed significant changes in antioxidant enzyme activities, with DM exposure increasing superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities, while decreasing catalase (CAT) and glutathione peroxidase (GPX) activities. Immune-related gene expression demonstrated suppressed IgM, IgD, and IgZ levels, along with altered inflammatory responses, with both DM and DM + SMX exposure inducing pro-inflammatory cytokines. Finally, feeding behavior was significantly impaired in the DM group at the 3 min mark, while the DM + SMX group showed partial mitigation of this effect. These findings highlight the neurotoxic, immunotoxic, and behavioral effects of DM and SMX, and underscore the potential for chemical interactions to modulate toxicity in aquatic organisms.