Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder with prevalent hypertension that significantly contributes to the mortality in this patient population. Pre-clinical and clinical evidence suggests that anti-CD3 antibody therapy may attenuate the development of autoimmune diseases like SLE. However, it is unclear whether this treatment impacts the development of the prevalent hypertension associated with SLE. The present study was designed to determine whether anti-CD3 antibody treatment attenuates the progression of hypertension in female SLE mice with already established renal disease (albuminuria ≥100 mg/dL). Female SLE (NZBWF1) and control (NZW) mice were administered either an antibody to CD3ε, a component of the T cell receptor complex expressed on all T cells, or IgG antibody (isotype control) for up to 4 weeks (intranasal; 25 μg/week). Spleen weight was lower in SLE mice treated with anti-CD3 antibody than in IgG-treated SLE mice, suggesting that immune system hyperactivity is decreased. Circulating anti-dsDNA autoantibodies were increased in SLE mice compared to controls and were blunted in the anti-CD3-treated SLE mice. The development of hypertension was attenuated in anti-CD3 treated mice with SLE independently of changes in renal injury (assessed by urinary albumin). These data suggest anti-CD3 therapy during autoimmune disease may have added clinical benefit to attenuate cardiovascular risk factors like hypertension.