Purpose of review <p>Current knowledge on inflammatory and central pain-modulatory pathways as potential mechanisms linking sleep disturbances with pain, and the role of sex in modulating these pathways will be reviewed.</p> Recent findings <p>There is increasing evidence that the degree to which inflammatory and pain-modulatory pathways are affected by sleep disturbances are modulated by sex, with recent studies suggesting a greater pro-inflammatory response in males compared to females, and a stronger impairment of pain-inhibitory pathways in females compared to males.</p> Summary <p>Knowledge on sex-differential activations of pain pathways by sleep disturbances has important therapeutic implications and may require different mechanism-based therapies to treat pain in both sexes effectively. The development of specific therapeutics that complement traditional sleep-improving therapies has the potential to better mitigate pain associated with sleep disturbances and interrupt the transition to pain chronicity in both sexes.</p>