Purpose of review <p>This review examines the role of core body temperature as an active physiological modulator of synaptic plasticity across the circadian cycle and sleep–wake states, with a specific focus on their relevance for mental health. The aim is to integrate evidence from cellular and clinical neuroscience to clarify whether thermoregulatory dysregulation may contribute to plasticity alterations observed in psychiatric disorders.</p> Recent findings <p>Recent experimental work shows that even modest brain temperature fluctuations modulate neuronal excitability, neurotransmission, and the balance between long-term potentiation and long-term depression. Circadian and sleep-dependent temperature oscillations are tightly coupled to metabolic activity, neurovascular dynamics, and network states, supporting synaptic potentiation during wakefulness and renormalization during NREM sleep. Clinical studies increasingly report blunted or elevated core temperature rhythms in mood and psychotic disorders, although direct links to plasticity markers in humans remain elusive.</p> Summary <p>Collectively, current evidence supports that temperature may represent a biologically meaningful variable capable of modulating synaptic plasticity across time. Thermoregulatory dysregulation may therefore represent a transdiagnostic mechanism contributing to vulnerability and persistence of mental disorders, warranting targeted experimental investigation.</p>