Human papillomavirus vaccine (HPVv) is used worldwide for prevention of infection. However several reports link this vaccine, with immune-mediated reactions, especially with neurological manifestations. Our previous results showed that HPVv-Gardasil and aluminum-immunized mice developed behavioral impairments. Studies have shown a positive effect of phospholipid supplementation on depression and cognitive functions in mice. Therefore, our goal was to evaluate the effect of a dietary supplement on vaccine-induced depression. Sixty C57BL/6 female mice were immunized with HPVv-Gardasil, aluminum or the vehicle (n = 20 each group), and half of each group were fed 5 times per week with 0.2 ml of a dietary supplement enriched with phosphatidylcholine. The mice were evaluated for depression at 3 months of age, by the forced swimming test. Both the Gardasil and the aluminum-treated mice developed depressive-like behavior when compared to the control group. The HPVv-Gardasil-immunized mice supplemented with phosphatidylcholine significantly reduced their depressive symptoms. This study confirms our previous studies demonstrating depressive-like behavior in mice vaccinated with HPVv-Gardasil. In addition, it demonstrates the ability of phosphatidylcholine-enriched diet to attenuate depressive-like behavior in the HPVv-Gardasil-vaccinated mice. We suggest that phosphatidylcholine supplementation may serve as a treatment for patients suffering vaccine-related neurological manifestations. © 2016, Springer Science+Business Media New York.