Mercury (Hg) is well recognized as a highly toxic substance to fish. Nevertheless, little is known about the toxic effects of Hg on immune organs. In this study, we investigated histology, antioxidant status and immune response of the spleen and head kidney in yellow catfish following 6 weeks of exposure to environmentally relevant concentrations of inorganic Hg (2 and 10 μg l Hg ). As expected, Hg accumulation and histological injury in both tissues were observed. Meanwhile, Hg exposure induced oxidative stress, which increased antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities, glutathione content, anti-hydroxyl radical capacity and the expression of genes associated with antioxidant (sod1, cat, gpx1, nrf2 and mt) and stress (hsp70) responses in dose- and tissue-specific manners. In the spleen, the mRNA levels of immune-related genes (il-1β, il-8, tnf-α, il-10, tgf-β, lys and c3) were upregulated by Hg exposure. However, in the head kidney, upregulation of tnf-α, il-10 and tgf-β mRNAs and downregulation of il-1β and lys expressions were observed, while transcriptions of il-8 and c3 were remarkably upregulated only in the 2 μg l group. Overall, our study indicated that Hg exposure could result in Hg accumulation and thereby induced histological impairment, oxidative stress and immunotoxicity in immune organs of yellow catfish, but some enzymes and/or genes involved in antioxidant and immune systems would be activated to resist Hg -induced damage.