BACKGROUND This study aimed to investigate the association between levels of serum amyloid A (SAA) and the activity of systemic lupus erythematosus (SLE). MATERIAL AND METHODS The study included 135 patients with SLE, including 52 patients with active SLE and 83 patients with inactive SLE and 149 healthy controls. The degree of activity of SLE was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K). Serum SAA levels were measured using a Cobas 8000 c702 modular analyzer. RESULTS The levels of SAA were significantly increased in patients with active SLE compared with patients with inactive SLE (median IQR, 16.65 mg/L; range, 9.35-39.68 mg/L, and median IQR, 2.30 mg/L, range, 1.30-4.80 mg/L) (p<0.001). Levels of SAA were significantly correlated with the SLEDAI-2K scores, the erythrocyte sedimentation rate (ESR), and hypersensitive C-reactive protein (Hs-CRP) in patients with SLE (r=0.726, p<0.001; r=0.631, p<0.001; r=0.774, p<0.001, respectively). Multivariate logistic regression analysis showed that the SAA values were independently associated with active SLE when controlled for white blood cell (WBC) count, red blood cell distribution width (RDW), ESR, and Hs-CRP (OR=1.772; p=0.01; 95% CI, 1.101-2.851). Receiver operating characteristic (ROC) curve analysis for SAA was used to identify patients with active SLE with an area under the curve of 0.971, a sensitivity of 90.4%, and a specificity of 94.0%. CONCLUSIONS SAA levels were significantly correlated with disease activity in patients with SLE.