Objectives. To compare the baseline clinical manifestations, immunological features, disease activity and damage accrual in systemic lupus erythematosus (SLE) patients from two US Hispanic subgroups. Methods. A total of 105 Hispanic SLE patients from Texas (a population of Mexican or Central American ancestry) and 81 from the island of Puerto Rico (all Puerto Ricans) participating in a longitudinal study of outcome were examined. The socio-economic/demographic, clinical and immunological variables were obtained at the time of enrolment (T0). Disease activity was determined with the Systemic Lupus Activity Measure (SLAM), and disease damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). Disease activity was also determined at the time of diagnosis (TD). Results. At T0 Hispanics from Texas were younger than those from Puerto Rico (33.1 ± 12.0 vs 37.5 ± 11.6 yr, P = 0.0125). Both groups were similar with regard to gender distribution (92.4 vs 95.1% females) and disease duration (1.4 ± 1.4 vs 1.7 ± 1.3 yr). Hispanics from Texas were more likely to have serositis (60.0 vs 8.6%, P < 0.0001), renal involvement (41.0 vs 13.6%, P < 0.0001), psychosis (5.7 vs 0.0%, P = 0.0365) and thrombocytopenia (21.0 vs 3.7%, P = 0.0006). On the other hand, Hispanics from Puerto Rico were more likely to have photosensitivity (81.5 vs 41.0%, P < 0.0001), malar rash (65.4 vs 45.7%, P = 0.0074) and discoid rash (13.6 vs 2.9%, P = 0.0060). At baseline, the presence of anti-dsDNA antibodies was higher in Hispanics from Texas (69.5% vs 46.9%, P = 0.0018) while anti-Ro antibodies were more frequent in Hispanics from Puerto Rico (24.7 vs 11.4%, P = 0.0175). Mean SLAM scores at TD (12.9 ± 6.4 vs 9.1 ± 4.6, P < 0.0001) and T0 (10.9 ± 6.3 vs 6.6 ± 3.8, P < 0.0001) were significantly higher in Hispanics from Texas. Similarly, mean SDI scores at T0 were higher in Hispanics from Texas (0.67 ± 1.08 vs 0.26 ± 0.54, P = 0.0026). By stepwise Poisson regression, SDI scores were associated with older age, disease activity and ethnicity (Hispanics from Texas). Conclusions. Early in SLE, marked differences are observed between Hispanics from Texas and Puerto Rico. Higher disease activity, more major organ involvement, higher frequency of anti-dsDNA antibodies and more damage accrual occur in Hispanic lupus patients from Texas than in those from Puerto Rico.