Abstract Body (Do not enter title and authors here): Sleep is essential for heart health throughout the lifespan. Although poor sleep is linked to cardiovascular disease and all-cause mortality, there is little known about how chronic sleep disruption affects the heart. Because adequate oxygen delivery is necessary to sustain cardiac function, we hypothesized that sleep disruption suppresses myocardial perfusion, which over time, could impair mechanical performance. To test this, we examined how environmental noise, a major contributor to human sleep disruption, applied during the murine inactive/light phase (noise-induced sleep disruption; NISD) impacts sleep patterns and myocardial perfusion in C57BL/6N male mice. We surgically implanted EEG/EMG transmitters to quantify wake and sleep periods. After recovery and a baseline period (2d), mice were exposed to randomized noise (2,382–4,000 kHz; ≤103 db; ≤39 sec) between 6:00–18:00 (NISD group). Control mice underwent the same procedure, but without noise application. Sleep durations were measured at baseline, 1 d, 2 wk, and 4 wk. Relative to control mice, NISD showed fragmented sleep patterns with reduced sleep bout length (~17%; p=0.02) and increased sleep bout number (~26%; p=0.09) when normalized to respective baseline data, yet similar 24 hr total sleep duration (control: 11.6 ± 0.3 h, NISD: 11.4 ± 0.9 h; n=3–4/group, p=0.82). After 4 wk of NISD, myocardial perfusion and cardiac function were measured using contrast echocardiography and left ventricular pressure-volume recordings at baseline and following norepinephrine-mediated increases in cardiac work. In control mice, myocardial perfusion increased in proportion to increases in cardiac work; however, in the NISD group, the slope of the relationship between myocardial perfusion and cardiac work was significantly blunted (control: 0.0058 ± 0.002; NISD: 0.0002 ± 0.001; n=4–5/group, p=0.01). Echocardiography revealed increased left ventricular diameter (LVID_s, control: 2.2±0.2 mm, NISD: 2.6±0.2 mm; p=0.01), and two-dimensional speckle tracking showed a significant reduction in global longitudinal left ventricular strain (control: 19.5±2.5%, NISD: 16.4±0.8%; p=0.02) in NISD mice compared with controls, consistent with moderate systolic impairment following prolonged sleep disruption. Taken together, these data support the concept that environmental factors, via effects on sleep quality, can impact the regulation of blood flow to the heart and cardiovascular health.