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Objectives Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), characterised by unpredictable outcomes due to the absence of reliable biomarkers. This study aimed to evaluate whether changes in the N-glycosylation of IgG, C3, AGP, and the serum proteome over one year of treatment correlate with clinical and histological features of LN and predict renal outcomes.Methods Serum samples from 19 treatment-naïve patients with LN were collected at baseline and 12 months post-treatment, in conjunction with per-protocol repeat kidney biopsy. IgG (Fc, Fab, and total), C3, AGP, and total serum glycoproteins were isolated and analysed as either released N-glycans or N-glycopeptides using high-throughput glycanolytic approaches. Clinical and histological data were obtained at both time points, along with assessments of clinical and histological response at 12 months and long-term renal function.Results In total, we identified 21/243 increased N-glycosylation traits (2 total IgG, 5 IgG Fc, 6 IgG Fab, 4 serum glycoproteins, 4 AGP, and 1 C3) and 10/243 decreased N-glycosylation traits (7 total IgG, 2 IgG Fc, 1 IgG Fab) following treatment. Baseline AGP IORMIF1N5H6S2F1 N5H6S2F1 showed a positive correlation with eGFR both at baseline (r=0.64, P=0.005) and at 12 months (r = 0.51, P = 0.032). Among AGP N-glycosylation traits, IVORMI1N7H8S3 N7H8S3 (r=0.66, P=0.002; r=0.48, P=0.041, respectively), VORMI1N8H9S4 N8H9S4 (r=0.51, P=0.029; r=0.49, P=0.038, respectively), and VORMI1N8H9S4F1 N8H9S4F1 (r=0.48, P=0.039; r=0.49, P=0.034, respectively) significantly correlated with AI at baseline and at 12 months. Presence of cellular crescents at baseline positively correlated with three AGP N-glycosylation traits: IORMISORMIIA1N4H5S2 N4H5S2 (r=0.49, P=0.036), VORMII1N5H6S3F1 N5H6S3F1 (r=0.63, P=0.006), and VORMII1N4H5S2 N4H5S2 (r=0.48, P=0.046). Serum protein N5H4F1 at 12 months was associated with both clinical (OR=12.3; 95% CI=1.7–223.7; P=0.045) and histological (OR=3571; 95% CI=1.7–7702877; P=0.008) response to treatment. Delta of serum glycoprotein N5H5S1 was independently associated with poor long-term outcome (HR=-10.6; 95% CI=8.62E-13–0.96; P=0.049).Conclusions This study suggests that glycosylation changes over one year of treatment are associated with specific clinical and histological features and both short- and long-term renal outcomes in LN, warranting further investigation of glycans as potential biomarkers.