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Background: Pesticides are usually applied as mixtures, and their joint impacts can generate substantial toxicity to organisms. Although exposures to chemical pesticide mixtures make up most occurrences of pesticide exposures, minimal concern has been given to their combined toxicity and interplays to date. In the present study, endpoints of multiple levels were determined to examine the combined toxic impacts of phoxim and deltamethrin on zebrafish (Danio rerio). Results: Our study showed that the LC50 values of phoxim obtained over a 96-h exposure period for D. rerio during different life stages ranged from 0.24 (0.12–0.33) to 3.39 (2.58–4.86) µM, and those of deltamethrin ranged from 0.0041 (0.0031–0.0060) to 2.97 (1.56–4.69) µM. Combinations of phoxim and deltamethrin displayed synergistic effects on zebrafish embryos. The activities of T-SOD, Cu/Zn-SOD, POD, and CarE varied dramatically under most administrations of phoxim, deltamethrin, and phoxim + deltamethrin combinations relative to the baseline value. Nine genes, namely, Mn-sod, Cu/Zn-sod, cas3, dio1, tsh, ERα, vtg1, cyp17, and crh, related to antioxidation, cell apoptosis, immunity, and the endocrine system were altered to a greater degree under the mixture administration compared with the individual administrations. Conclusions: In summary, our current data offered a detailed insight into the combined toxic impacts of pesticide mixtures at various endpoints and over a wide range of concentrations. The results emphasized the necessity to consider the administration mixtures during the ecological risk assessment of pesticides. [ABSTRACT FROM AUTHOR]