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Abstract Aim The objective of this study was to evaluate the potential of hydrogen in preventing and treating psychiatric symptoms, particularly depressed mood and loss of interest, and to explore its underlying mechanisms. A mouse model exhibiting inflammation‐derived depressive symptoms was used for the investigation. Methods Institute of Cancer Research mice were subjected to a 7‐day intervention of either 30% hydrogen or 40 g per day of air via jelly intake. On the final day, lipopolysaccharide (LPS) was intraperitoneally administered at 5 mg/kg to induce inflammation‐related depressive symptoms. Behavioral and biochemical assessments were conducted 24 h post‐LPS administration. Results Following LPS administration, a decrease in spontaneous behavior was observed; however, this effect was mitigated in the group treated with hydrogen. The social interaction test revealed a significant reduction in interactions with unfamiliar mice in the LPS‐treated group, whereas the hydrogen‐treated group exhibited no such decrease. No significant changes were noted in the forced‐swim test for either group. Additionally, the administration of LPS in the hydrogen group did not result in a decrease in zonula occludens‐1, a biochemical marker associated with barrier function at the cerebrovascular barrier and expressed in tight junctions. Conclusion Hydrogen administration demonstrated a preventive effect against the LPS‐induced loss of interest, suggesting a potential role in symptom prevention. However, it did not exhibit a suppressive effect on depressive symptoms in this particular model. These findings highlight the nuanced impact of hydrogen in the context of inflammation‐induced psychiatric symptoms, indicating potential avenues for further exploration and research.