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Cerebrospinal fluid (CSF) oligoclonal band (OCB) analysis is central to the diagnostic evaluation of neuroinflammatory diseases of the central nervous system (CNS), yet its reliance on lumbar puncture limits utility in screening and longitudinal monitoring. Serum metabolomics provides a minimally invasive approach to capture peripheral correlates of intrathecal immune activity. This study extends our previous two-group comparison by incorporating all five classical OCB patterns to delineate serum metabolic gradients associated with varying degrees of intrathecal immunoglobulin synthesis. A total of 92 adults undergoing diagnostic evaluation for suspected CNS inflammatory disorders were stratified by OCB Type (1–5). Serum samples were analysed using targeted ¹H-NMR spectroscopy on a Bruker Avance Neo 600 MHz platform and processed with Bruker’s IVDr pipeline. Statistical analyses included Kruskal–Wallis testing with FDR correction, PCA, PLS-DA with VIP scoring, and ROC-AUC modelling. Six metabolites exhibited significant or near-significant differences, led by Leucine (p = 0.0047, q = 0.073) and 2-Oxoglutaric acid (p = 0.0022, q = 0.069). PLS-DA identified five key discriminators with VIP > 1.5: Leucine, 2-Oxoglutaric acid, Histidine, Valine, and Glycine. A combined logistic model (Leucine + Histidine + Citric acid) achieved an AUC of 0.83 for distinguishing OCB Type 1 from Type 2. This first targeted serum ¹H-NMR metabolomic evaluation across all OCB patterns reveals a graded biochemical trajectory reflective of intrathecal immune activation. Amino-acid and TCA-cycle intermediates emerge as promising minimally invasive candidates for neuroinflammatory stratification and precision evaluation beyond traditional MS paradigms.