Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement. Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy. Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10(-6)), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, rho = 0.37, p < 10(-4)), C-reactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 x 10(-3) for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare. Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN.