Background: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, particularly the kidneys. Interleukin (IL) biomarkers including IL-10 and IL17/23 axis play an important role in SLE pathogenesis. Objectives: To investigate the predictive value of IL-17, IL-23, and IL-10 biomarkers in detecting lupus nephritis (LN) class in SLE cases. Methods: This is a case-control study involving 160 individuals: 100 patients with SLE (80 LN patients who had a recent report of kidney biopsy in the two months prior to the study +20 non renal SLE patients), and 60 age- and sex-matched healthy volunteers. All participants were subjected to clinical and laboratory studies, as well as the evaluation of their IL-17, IL-23, and IL-10 biomarkers. Results: IL-17, IL-23, and IL-10 were significantly elevated in SLE patients (p-value < 0.001), especially in cases with high disease activity (p-value < 0.001). Moreover, these biomarkers were considerably higher in LN patients (p-value < 0.001), particularly among class III and IV LN (p-value < 0.001) and in cases with high nephritis activity index (p-value < 0.001). ROC curve analysis revealed precise cutoff points of IL-17, IL-23, and IL-10 levels in each renal histopathological class with high sensitivity and specificity. Conclusion: IL-17, IL-23, and IL-10 biomarkers are higher in SLE patients and are correlated with SLE Disease Activity Index (SLEDAI). They are more prevalent in individuals with LN, particularly in cases with high activity index and with more aggressive classes (in renal classes III and IV). These biomarkers might function as indicators for detecting LN activity and as predictors of LN class.