Abstract Background Chronic obstructive pulmonary disease (COPD) affects up to 10% of Canadians. Patients with COPD may present with secondary humoral immunodeficiency as a result of chronic disease, poor nutrition or frequent courses of oral corticosteroids; decreased humoral immunity may predispose these patients to mucosal infections. We hypothesized that decreased serum immunoglobulin (Ig) levels was associated with the severity of an acute COPD exacerbations (AECOPD). Methods A prospective study to examine cardiovascular risks in patients hospitalized for AECOPD, recruited patients on the day of hospital admission and collected data on length of hospital stay at index admission, subsequent emergency department visits and hospital readmissions. Immunoglobulin levels were measured in serum collected prospectively at recruitment. Results Among the 51 patients recruited during an admission for AECOPD, 14 (27.5%) had low IgG, 1 (2.0%) low IgA and 16 (31.4%) low IgM; in total, 24 (47.1%) had at least one immunoglobulin below the normal range. Patients with low IgM had longer hospital stay during the index admission compared to patients with normal IgM levels (6.0 vs. 3.0 days, p = 0.003), but no difference in other clinical outcomes. In the whole cohort, there was a negative correlation between serum IgM levels and length of hospital stay (R = − 0.317, p = 0.024). There was no difference in clinical outcomes between subjects with normal and low IgG levels. Conclusion In patients presenting with AECOPD, low IgM is associated with longer hospital stay and may indicate a patient phenotype that would benefit from efforts to prevent respiratory infections. Trial registration statement: Retrospectively registered.