Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disease that predominantly affects women during their reproductive years. While women with SLE have hypertension, the underlying mechanisms for this have not been examined. Despite the fact that inflammation is associated with altered endothelial and vascular function, the role of altered vascular function in the development of hypertension during SLE is unclear. In the present study, we tested whether a mouse model of SLE (NZBWF1) develops hypertension and examined whether increased blood pressure was associated with impaired endothelial dependent relaxation. Female NZBWF1 Mice were studied at 8, 20, and 36 weeks of age. By 36 weeks, urinary albumin and anti-nculear antibodies were increased in SLE compared to control mice. Mean arterial pressure, measured by radio-telemetry, was significantly increased in SLE mice (124 ± 4 mmHg, n= 10) compared to control NZW/LacJ mice (111 ± 3 mmHg, n=7) at 36 weeks. Isolated carotid arteries from NZBWF1 mice, pre-contracted with U46619 for assessment of endothelial dependent relaxation, demonstrated a progressively impaired relaxation to acetylcholine with age, although eNOS mRNA expression was not different. Maximal tension generated by 5-hydroxytryptamine (5-HT) was increased in carotid arteries from NZBWF1 mice compared to controls at 8, 20, and 36 weeks of age suggesting a role for altered vascular function early on in the progression of SLE. Taken together our data support a role for altered endothelial function as a contributing factor to the development of hypertension during SLE.