Cytotoxic CD8⁺ T-cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the role of CD107a (LAMP-1) on cytotoxic CD8⁺ T-cells in SLE-patients in particular with lupus nephritis. Peripheral blood of SLE-patients (n = 31) and healthy controls (n = 21) was analyzed for the expression of CD314 and CD107a by flow cytometry. Kidney biopsies of lupus nephritis patients were investigated for the presence of CD8⁺ and C107a⁺ cells by immunohistochemistry and immunofluorescence staining. The percentages of CD107a⁺ on CD8⁺ T-cells were significantly decreased in SLE-patients as compared to healthy controls (40.2 ± 18.5% vs. 47.9 ± 15.0%, p = 0.02). This was even more significant in SLE-patients with inactive disease. There was a significant correlation between the percentages of CD107a⁺CD8⁺ T-cells and SLEDAI. The evaluation of lupus nephritis biopsies showed a significant number of CD107a⁺CD8⁺ T-cells mainly located in the peritubular infiltrates. The intrarenal expression of CD107a⁺ was significantly correlated with proteinuria. These results demonstrate that CD8⁺ T-cells of patients with systemic lupus erythematosus have an altered expression of CD107a which seems to be associated with disease activity. The proof of intrarenal CD107a⁺CD8⁺ suggests a role in the pathogenesis of lupus nephritis.