Hematuria or sterile pyuria as isolated urinary findings present a clinical dilemma for the treating physician. Our objective was to determine whether isolated hematuria and isolated sterile pyuria are associated with active systemic lupus erythematosus (SLE) with respect to renal and non-renal disease activity. This is a descriptive study from a large SLE cohort followed prospectively at the University of Toronto Lupus Clinic. All episodes of isolated hematuria and isolated pyuria between 1970 and 2000 were identified from our database. Isolated hematuria was defined as > 5 red blood cells per high power field; isolated sterile pyuria was defined as > 5 white blood cells per high power field in the absence of urinary infection and other renal manifestations. Non-renal disease activity (defined as nrSLEDAI > 1) was determined at first episode of isolated hematuria and pyuria. Renal disease activity was assessed by scoring renal biopsies within 3 months of detecting isolated hematuria or sterile pyuria. Thirty-four percent (323/946) of our cohort had at least one episode of isolated hematuria. Seventy-seven percent of these patients had concurrent non-renal disease activity. Of the 22 biopsies scored with isolated hematuria, 96% were abnormal (WHO > class I), including 52% with active nephritis. Twenty-three percent (215/946) had at least one episode of isolated sterile pyuria. Seventy-eight percent of these patients had concurrent non-renal disease activity. All 12 biopsies scored with isolated pyuria were abnormal (WHO Class > 1), including 75% with active nephritis. The appearance of isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. An ongoing debate has emerged regarding the significance of isolated hematuria and isolated pyuria with respect to SLE disease activity. The results of this study suggest that isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. Thus isolated hematuria and isolated sterile pyuria should be considered manifestations of active SLE.