Increased free light chain (FLC) levels have been reported as useful in various autoimmune conditions. We investigated how FLC concentrations change upon B cell targeted therapy in systemic lupus erythematosus (SLE) patients and if they correlate with disease activity. We retrospectively studied 11 SLE patients without renal failure, whom were treated with rituximab. Quantitative determination of IgG, IgA, IgM, and serum FLC was performed before and after rituximab. At baseline, 70% had abnormal serum FLC levels, including increased kappa and lambda levels, while the kappa/lambda ratio was normal for all. A strong correlation was observed between complement C3 fraction and kappa levels (r = -0.929, P < 0.001) or lambda levels (r = -0.854, P = 0.003), but not with IgG, IgA, or IgM levels. After rituximab treatment, kappa and lambda FLC concentrations decreased significantly whilst total concentrations of IgG, IgA, and IgM also decreased but remained within the normal range. There was a strong correlation only between kappa FLC levels and complement C3 fraction consumption (r = -0.543, P = 0.003). In SLE patients without renal failure, increased FLC levels (mainly kappa) with normal kappa/lambda ratios are a common feature, and in contrast to total IgG levels, FLC concentrations correlate with biological disease activity.