Objective: Chronic obstructive pulmonary disease is a progressive inflammatory lung disease characterized by chronic bronchitis and emphysema. This study aimed to evaluate the levels of composite inflammatory markers, including systemic immune-inflammation index, systemic inflammatory response index, pan-immune-inflammation value, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, hemoglobin-to-red cell distribution width ratio, hemoglobin-to-monocyte ratio, and hemoglobin-to-white blood cell count ratio, in patients presenting with acute exacerbation of chronic obstructive pulmonary disease. Methods: This retrospective observational study included patients aged ≥40 years who presented to a tertiary Chest Diseases clinic between 2022 and 2024 with acute exacerbation of chronic obstructive pulmonary disease. Patients were categorized into two groups (outpatient treatment and hospitalization groups) according to the management strategy used. Hematological parameters and composite inflammatory indices were calculated and compared between the groups. Results: In total, 314 patients were included; 80.3% of them were male. Hospitalized patients were significantly older and had higher white blood cell counts, C-reactive protein levels, neutrophil-to-lymphocyte ratios, platelet-to-lymphocyte ratios, systemic immune-inflammation indices, systemic inflammatory response indices, and pan-immune-inflammation values than outpatients (all p < 0.001). In contrast, the hemoglobin-to-red cell distribution width, hemoglobin-to-monocyte, and hemoglobin-to-white blood cell count ratios were significantly lower in hospitalized patients (all p < 0.001). Conclusions: Composite inflammatory indices derived from routine blood tests may reflect the systemic inflammatory burden during acute exacerbation of chronic obstructive pulmonary disease and may support the clinical assessment of hospitalization risk.