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Background: Kidney involvement is prevalent in systemic lupus erythematosus (SLE) and is the leading cause of disability and death. Colony-stimulating factor-1 (CSF-1) may be involved in the development of lupus nephritis (LN). This study aimed to evaluate serum CSF-1 levels in SLE patients with and without proteinuria and its correlation with the value of proteinuria. Methods: A total of 75 subjects including 25 newly diagnosed SLE cases without renal involvement evidence, 25 new SLE with biopsy-proven LN, and also, 25 healthy controls were included in the study. Serum CSF-1 level was measured in all participants using a human CSF-1 ELISA kit. Results: Analysis of variance (ANOVA) and post hoc analysis demonstrated significant differences between the three groups including healthy individuals, and SLE subjects with and without nephritis (P=0.006). The mean values of CSF-1 levels were increased among both participants without LN and patients with LN, compared to healthy individuals. However, a statistically significant greater mean concentration of CSF-1 was detected in individuals with LN compared to the healthy group (P=0.004). No significant statistical correlation was found between CSF-1 and 24-hour urine protein. Furthermore, when comparing the activity of SLE, a notable distinction was observed in the SLE disease activity index (SLEDAI) values between individuals with and without proteinuria (P<0.0001). Conclusion: An upward trend in average CSF-1 levels was observed among both patients with and without LN, in comparison to healthy individuals. Significantly enhanced concentrations of CSF-1 were found in subjects with LN compared to healthy individuals. [ABSTRACT FROM AUTHOR]