Abstract Body: The Western diet, high in saturated/trans fats, refined sugars, and low in fiber, drives the current epidemic of obesity and related cardiovascular risks, including hypertension. In animal studies, high-fat diet (HFD) and high-fat high-sucrose diet (HFHSD) are commonly used to model human obesity. Both induce weight gain, increased adiposity, and metabolic dysfunction, but their comparative effects on cardiovascular outcomes remain unclear. We assessed sympathetic and cardiovascular responses to HFD and HFHSD, using normal chow diet (NCD) as control, in C57BL/6J mice. Male mice (5 weeks old) were fed NCD, HFD, or HFHSD for 16 weeks. Both HFD and HFHSD led to significantly greater weight gain (28±1g each) vs. NCD (12±1g). Fat mass, glucose tolerance, and insulin sensitivity were similarly impaired in both diet groups compared to NCD group. Blood pressure (BP, telemetry) was significantly elevated in HFD and HFHSD mice vs. NCD, with no difference between diets (nighttime systolic BP: 135±2 in HFD, 136±1 in HFHSD, 122±1 mmHg in NCD; daytime: 123±1, 126±2, and 112±2 mmHg, respectively). Heart rate was similarly and significantly increased in both groups. Regional sympathetic nerve activity (SNA) was elevated in HFD and HFHSD vs. NCD, but with nerve-specific differences: renal SNA was higher in HFD (149±10 spikes/s) vs. HFHSD (99±12 spikes/s) and NCD (65±5 spikes/s); lumbar SNA was higher in HFHSD (145±9 spikes/s) vs. HFD (114±9 spikes/s) and NCD (91±6 spikes/s); splanchnic SNA was similarly increased in both. Baroreflex sensitivity was significantly reduced in HFD and HFHSD vs. NCD. Echocardiography showed increased cardiac mass, left ventricular wall thickness, and left atrial diameter in both diets, but cardiac output was increased only in HFHSD. Endothelium-dependent vasodilation (acetylcholine following phenylephrine-induced contraction) was impaired in both diet groups; endothelium-independent vasodilation (sodium nitroprusside) was impaired only in HFHSD. These findings show that both HFD and HFHSD elevate BP, increase SNA, impair baroreflex function, and promote cardiovascular dysfunction, with HFHSD inducing distinct features. These results highlight the cardiovascular harm of Western dietary patterns.