We performed a retrospective study of 10 patients with refractory systemic lupus erythematosus treated with rituximab to determine the efficacy, safety and impact on hospitalization days. Patients received rituximab according to a standardized protocol, all achieved B-cell depletion with clinical improvement in nine patients. At 12 months, BILAG scores improved significantly from a median of 13.5 (range 3-20) at baseline to 1 (range 0-27) (p < 0.05). There was significant reduction in urinary total protein excretion with stabilization of renal function in patients with nephritis. Two out of three patients with thrombocytopenia had normalization of platelet counts. The median duration of B-cell depletion was 6 months (range 6-18). Two patients required retreatment and responded well. There were no adverse outcomes following rituximab therapy. Patients with lupus nephritis spent a median of 17.1 days per year (range 1.9-49) in hospital on conventional treatment which was reduced to 0 days (range 0-14.8, p = 0.027) post-rituximab treatment. The cost of hospitalization was 5989 Singapore dollars per patient-year while on conventional treatment and 5792 Singapore dollars per patient-year post-rituximab. This study adds to the growing literature of rituximab efficacy with potential cost saving in lupus nephritis.