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Exposure to persistent mild stress is a frequently encountered chronic challenge in a rapidly evolving society. Depending on various factors including sex, the response to stressors varies and is closely linked to the phenomenon of resilience. Depression and anxiety can be considered maladaptive responses to such stress. In this rat study, we investigated the sex-dependent effects of low-grade systemic inflammation during 1 week in combination with chronic unpredictable mild stress during the following 4 weeks on anxiety-like behavior and episodic feeding behavior. Increased anxiety-like behavior and increased sucrose intake were identified in stressed compared to control animals regardless of sex. Interestingly, two nearly equally distributed subpopulations were found in the stressed groups within each sex at the end of the 5-week protocol of combined stress exposure: the resistant and the susceptible, which were characterized by unchanged and increased sucrose intake, respectively. This difference in susceptibility to protracted combined mild stress and ensuing response to a sucrose eating binge demonstrates the complexity of the underlying regulatory mechanisms associated with emotional hyperreactivity. This model carries the potential for further investigation of the molecular basis of resilience and susceptibility to combined stressors and for testing treatments with potential preventive or therapeutic effects., (© 2024. The Author(s).)