We stratified patients with SLE into low disease activity (SLEDAI < 6) and high disease activity (SLEDAI ≥ 6) groups, and S100A8 levels in all biofluids were significantly higher in the high disease activity group (serum, 2,052.6 ± 1,326.8 vs. 1,659 ± 1,107.9 pg/ml, p = 0.011; urine, 2,231.5 ± 2,396.6 vs. 1,638 ± 1,483.8 pg/ml, p = 0.02; and saliva, 487,263 ± 640,283.6 vs. 68,610.5 ± 91,553.7 pg/ml, p < 0.001). Here, S100A8 is linked to systemic lupus erythematosus.