Although the significance of inflammatory cytokines and chemokines in the pathogenesis of SLE is well established, the findings showed diversity and implied that combining different biomarkers could be useful in monitoring disease activity or organ involvement. Despite the potentially high prevalence of lung involvement in SLE, only a few studies have investigated for lung biomarkers. The aim of this study was to assess the value of Chemokine Ligand 21 (CCL 21) and Interferon gamma-induced protein 10 (IP10) as serum biomarkers for pulmonary involvement in SLE and their correlation with disease activity, organ involvement, pulmonary function tests (PFTs), and chest CT findings. Sixty SLE patients and 30 age- and sex-matched controls were enrolled into this study. All patients underwent serological tests, PFTs, and chest CT examination. The serum levels of CCL21 and IP10 were analyzed, and their correlations with PFTs and CT were explored. SLE patients with pulmonary involvement had higher serum CCL21 and IP10 levels compared to those without pulmonary involvement which in turn had higher levels than the controls. There were strong negative correlations between CCL21 and IP10 and FEV1, FVC, and DLCO. There were also strong correlations between both biomarkers and HRCT and pulmonary damage, but no correlation with other disease manifestations. Serum level of 2095pg/mL for CCL21 and 7185pg/mL for IP10 could detect pulmonary involvement in SLE with a sensitivity of 83.7% and a specificity of 94.1%. Both biomarkers performed equally well in detecting SLE pulmonary involvement with a strong agreement between them (κ = 0.86, p < .001), but CCL21 was better correlated with PFT abnormalities. Both CCL21 and IP10 are serum biomarkers to detect pulmonary involvement in SLE with high sensitivity and specificity. CCL21 correlates better with PFT abnormalities.