Abstract Body: Inadequate sleep disrupts circadian clock function and impacts blood pressure (BP) diurnal rhythms, contributing to increased cardiovascular risk. Sleep disturbances are common during menopause, but whether they worsen menopause-associated BP dysregulation remains unclear. To address this, we examined how sleep restriction (SR) affects BP rhythms in a mouse model of menopause and in postmenopausal women. Female C57BL/6J mice were either intact or ovariectomized (OVX) at 8 weeks of age and implanted with radiotelemetry devices. After baseline BP and pulse wave velocity (PWV) measurements via high-resolution ultrasound, mice underwent SR (3 h sleep opportunity) for two weeks via a multiple-platform protocol. OVX mice exhibited disrupted 12-hour BP rhythms and a non-dipping phenotype (intact: 11 ± 0.7% vs. OVX: 7.8 ± 0.8%, p=0.01). In OVX but not intact mice, SR further reduced dipping (4 ± 0.8%) and increased PWV (2.2 ± 1 vs. 3.5 ± 1.5 m/s, p=0.007). Carotid arteries assessed via biaxial pressure myography showed increased material stiffness in OVX versus intact mice which was exacerbated by SR in both groups. Uterine weights were significantly reduced in intact-SR mice, indicating an impact of SR on estrogen signaling. A separate cohort of intact and OVX mice underwent the same protocol and were euthanized at ZT0 or ZT12 for aortic RNA-seq and GPER1 expression. RNA-seq revealed downregulation of core circadian genes during the day in OVX mice. GPER1 expression followed a circadian pattern in intact aortas (light: 18 ± 3.7 vs. dark: 40.2 ± 12 copies/ng RNA) and was reduced at night in OVX mice (24.6 ± 10 copies/ng). In nine postmenopausal women from the SLEEP-IN study, compared to habitual sleep, SR (3.5–4 h/night for three nights) unexpectedly reduced daytime BP (120 ± 3.3 vs. 115 ± 3.3 mmHg; p=0.002) and did not affect nocturnal dipping (11 ± 3.1% vs. 9.7 ± 3.0%; p=0.61). Our findings from an animal model indicate that estrogen loss and sleep restriction together disrupt circadian BP regulation and exacerbate vascular dysfunction. However, clinical data using a shorter SR protocol did not emulate the dipping phenotype in mice. In conclusion, our findings show that ovarian hormones provide protection from circadian disruption in female mice. Exploiting the relationship between circadian and estrogen signaling may provide therapeutic benefits in aging women.