<p>Sleep-onset insomnia, characterized by difficulty falling asleep, is linked to increased health risks. Previous studies have shown that the central amygdala (CeA) plays a crucial role in stress regulation, with the somatostatin neurons in the CeA (CeA^SST+) involved in adaptive stress responses. However, the role of CeA^SST+ neurons in stress-induced sleep-onset insomnia remains unclear. In this study, we found that the activity of CeA^SST+ neurons is closely associated with stressful events using fiber photometry in mice. Acute optogenetic activation of CeA^SST+ neurons induced a rapid transition from non-rapid eye movement (NREM) sleep to wakefulness. Semi-chronic optogenetic and chemogenetic activation of CeA^SST+ neurons led to prolonged sleep-onset latency and increased wakefulness. Chemogenetic inhibition of these neurons ameliorated sleep-onset insomnia induced by stressful stimuli, but did not affect sleep-wake behavior under physiological conditions. Collectively, our results suggested that CeA^SST+ neurons are a key neural substrate for modulating stress-induced sleep-onset insomnia, without influencing physiological sleep. These findings highlight CeA^SST+ neurons as a promising target for treating stress-related sleep-onset insomnia in clinical practice.</p>