<p>Melatonin (C₁₃H₁₆N₂O₂), a naturally occurring indoleamine, is a versatile molecule found in unicellular as well as in multicellular organisms, including both non-chordates and chordates. Teleost melatonin is secreted from the pineal gland, which functions as a synchronizer of the circadian rhythm. The present study focused on deciphering the immune-modulatory role of melatonin in a snakehead teleost, <i>Channa punctatus</i>. Two doses of melatonin (2 and 5&#xa0;μg/g body weight) were administered intramuscularly in the fish for 10 and 20&#xa0;days. Respiratory burst activity of spleen and anterior kidney cells was measured through nitroblue tetrazolium assay, while nitric oxide production was evaluated indirectly by nitrite assay. The phagocytic response of macrophages was also measured using yeast (<i>Saccharomyces cerevisiae</i>) cells. Apart from innate immune functioning, the adaptive immune status of the fish was also evaluated through mitogen-stimulated lymphocyte proliferation. We found that melatonin modulated the immune responses of spleen and anterior kidney cells differentially, with dose- and duration-dependent effects. It seemed that the cells responded to melatonin differentially, where some immune parameters, such as superoxide and nitrite production, were elevated, while others, like phagocytosis, were unaltered. It is concluded that melatonin augments the immune functions of cells from lymphoid organs in different ways.</p>