Objective: We investigated the association of serum and urine beta 2-microglobulin (beta 2MG) with renal involvement and clinical disease activity in systemic lupus erythematosus (SLE). Methods: Sixty-four female patients with SLE were enrolled. We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine beta 2MG levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the SLEDAI scores, two groups were categorized: low (0-5 of SLEDAI) and high (6-19 of SLEDAI) disease activity groups. The presence of renal involvement was determined by renal SLEDAI score. Statistical analysis was performed using Spearman's correlation analysis, Mann-Whitney U test, multivariate regression analysis, and logistic regression analysis. Results: Urine beta 2MG levels were significantly different between low and high SLEDAI groups (p = 0.001), but not for serum beta 2MG levels (p = 0.579). Patients with renal involvement showed higher urine beta 2MG levels compared to those without renal involvement (p < 0.001), but again there was not a difference in serum beta 2MG levels (p = 0.228). Urine beta 2MG was closely associated with SLEDAI (r = 0.363, p = 0.003), renal SLEDAI (r = 0.479, p < 0.001), urine protein/Cr (r = 0.416, p = 0.001), and ESR (r = 0.347, p = 0.006), but not serum beta 2MG (r = 0.245, p = 0.051). Urine beta 2MG level was identified as a surrogate for renal involvement (p = 0.009, OR = 1.017, 95% CI 1.004-1.030) and overall disease activity (p = 0.009, OR = 1.020, 95% CI 1.005-1.036). Conclusions: We demonstrated that urine beta 2MG levels are associated with renal involvement and overall clinical disease activity in SLE.