Objectives Most research evaluating the effect of menopause on mental health focuses on depression. However, short-term positive and negative emotional well-being are also key aspects of mental health. The domino hypothesis posits that vasomotor symptoms (VMS) impact mental health through sleep disturbance (SD). Thus, we evaluated SD as a mediator of the association of VMS with positive and negative emotional well-being in midlife women, using both subjective and objective measures of VMS and SD. Study design Midlife women (N = 242; 98% postmenopausal; mean age 59.02 ± 4.43 years) enrolled in MsBrain I underwent 72 h of at-home monitoring of VMS, SD, and positive and negative emotional well-being. Main outcome measures Nighttime VMS frequency measured via self-report and sternal skin conductance. SD (i.e., wake after sleep onset) measured via self-report and actigraphy. Positive and negative emotional well-being measured via ecological momentary assessment methods. Results In structural equation modeling of subjective symptoms, there was an indirect effect of higher nighttime VMS frequency on lower positive (b = −0.086, p < .05) and higher negative (b = 0.084, p  0.05). Only greater objectively assessed SD was associated with lower positive emotional well-being (b = −0.851, p < .05). Conclusions Higher nighttime VMS frequency was indirectly associated with worse short-term emotional well-being through greater SD, but only when VMS and SD were measured subjectively. Greater objective SD was associated with lower positive emotional well-being only. Therefore, subjective and objective SD may be targeted to enhance the short-term emotional well-being of midlife women.