Background Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) have emerged as important biomarkers in multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD). However, their interest in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) remains unclear. Our aim was to characterise sNfL and sGFAP profile and analyse their usefulness in predicting relapses and disability in MOGAD. Methods Retrospective study of adult MOGAD patients with serum samples collected at baseline (≤3 months from disease onset) and follow-up (>6 months from baseline sample). sNfL and sGFAP were analysed using Simoa HD-1, and values were compared across time-points. The association between biomarkers and clinical variables and their predictive value for disability and relapses were analysed. Results Eighty-nine MOGAD patients were included. Baseline sNfL and sGFAP values were high at baseline and decreased over time (p<0.001, p=0.027, respectively). sNfL and sGFAP values were associated with Expanded Disability Status Scale (EDSS) at attacks (β 0.15 (0.06; 0.25), p=0.002; β 0.14 (0.07; 0.21), p<0.001, respectively) and were lower in optic neuritis presentations (β −0.69 (−1.18; −0.19), p=0.007; β −0.42 (−0.76; −0.08), p=0.016). Biomarker deltas[Δ] (baseline values – second samples values) were associated with ΔEDSS (initial EDSS - final EDSS) (ΔsNfL β 0.52 (0.01; 1.04), p=0.046; ΔsGFAP β 1.07 (0.38; 1.75), p=0.003). Finally, sNfL values independently predicted the risk of relapses (HR 2.06 (1.41; 3.01), p<0.001). Conclusions Our results on sNfL and sGFAP suggest initial neuro-axonal and astrocytic damage in MOGAD and the utility of these biomarkers at onset and follow-up in predicting clinical recovery and relapses.