This study was designed to evaluate the effect of quercetin, a natural flavonoid, on behavioral alterations, brain oxidative stress, and immune dysregulation caused by a chemotherapeutic agent, Adriamycin (ADR; 7 mg/kg of body weight). Different subsets of male Wistar rats were used to determine the benefit of quercetin on ADR-related depression-like and anxiety-like behaviors in the forced swim test, open field, and elevated plus maze, respectively. Quercetin (60 mg/kg of body weight) was administered 24, 5, and 1 h before the test session of forced swim test (FST) or at the same time points before the elevated plus maze/open field (EPM/OF) tests. Other subsets of rats were sacrificed after quercetin injections to assess the plasma corticosterone level, the brain oxidative status, and the immune cell count. Our results indicate that quercetin alleviated the anxio-depressive-like behavior, attenuated the brain oxidative stress, and suppressed the corticosterone excess that appeared following ADR treatment. The ADR-induced immune disturbance was slightly diminished after quercetin administration, especially for the lymphocyte count. This study suggests that quercetin can mitigate the neurobehavioral and immunological impairments that manifest in ADR-treated rats. Therefore, the combination of quercetin treatment with the chemotherapeutic regimen seems to be beneficial against chemotherapy-related complications.