Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. The purpose of this study was to examine the clinical and immunological characteristics associated with LN development during the course of SLE in Colombians. Therefore, patients with SLE followed at five different referral centers in Medellin, Bogota, and Cali were included in this cross-sectional and multicenter study. Factors influencing LN were assessed by conditional logistic regression analysis, adjusting by gender, age at onset, duration of disease, and city of origin. The entire sample population included 467 patients, of whom 51% presented with LN. The presence of anti-dsDNA antibodies (adjusted odds ratio (AOR), 2.06; 95% confidence interval (CI), 1.16-3.65), pleuritis (AOR, 3.82; 95% CI, 1.38-10.54), and hypertension (AOR, 2.63; 95% CI, 1.23-5.62) were positively associated with LN, whereas the presence of anti-La antibodies was a protective factor against LN development (AOR, 0.4; 95% CI, 0.19-0.85). A review of literature on LN in different populations is made. The identified clinical- and laboratory-associated factors would assist earlier diagnosis and guide decisions on therapeutic interventions on this critical and frequent complication of SLE.