Nausea in rodents is challenging to recognize because they cannot vomit. Sedation, anesthesia, and antibiotic therapy are frequently performed in chinchillas; however, these interventions often will lead to a substantial reduction in food intake, which has been suggested to be related to nausea. Anti-nausea medications such as maropitant and ondansetron are used safely and effectively to mitigate nausea following anesthesia or drug administration in dogs and cats. Therefore, the objective of this study was to determine the safe and effective dosages of maropitant and ondansetron in chinchillas with experimentally induced hyporexia. Dexmedetomidine-midazolam or oral metronidazole were used to induce hyporexia, and both models have been previously validated within our laboratory. Maropitant (1 and 4 mg/kg SC) and ondansetron (0.5 and 2 mg/kg SC) were evaluated as single doses in two randomized, controlled, blinded, complete cross-over studies employing the sedation model. In a third randomized, controlled, blinded, complete cross-over study, oral metronidazole was used to induce hyporexia. Ondansetron (0.5 mg/kg SC) and maropitant (4 mg/kg SC) were administered once daily for three consecutive days in this study. Daily assessments of food intake and fecal output were conducted to evaluate the efficacy and safety of the drugs. Findings indicate that both maropitant and ondansetron were safe, with no clinically significant effects on food intake observed in both the sedation and metronidazole models. The results of this study will provide clinicians with evidence-based guidance for the management of hyporexia and nausea in chinchillas.