The intricate link between physiology and seasonal mood changes remains elusive, whereas brain neurotransmitter signaling seems to stand at the central stage. It is recently disclosed that the endogenous opioid signaling demonstrates seasonal patterns, as is predominant in the brain socio-emotional circuits and also, peripherally in tissues crucial for energy homeostasis. Compared to other types of neurotransmissions, such as the serotonin signaling, brain opioid signaling is thought to have a top-tier role in sociality. Further, the endogenous opioid is a neuropeptide with large molecular mass. In contrast to the faster response of small molecular neurotransmitter signaling, the neuropeptide signaling is characterized with slower response and more sustained effects, favoring a potential role in the low speed of seasonal mood changes. In the current chapter, potential roles of central and peripheral opioid receptor signaling, as well as relevant body-brain interactions, inducing seasonal affective disorders are discussed.