This study aims to explore the effect of noninvasive ventilation combined with vitamin D in acute exacerbation of chronic obstructive pulmonary disease. Ninety-eight patients admitted to Mengcheng County NO.1 People’s Hospital were included. The control group received comprehensive treatment, including bronchodilators, glucocorticoids, antibiotics, and expectorants, correction of water and electrolyte imbalance, and nutritional support. Based on the control group, patients in the treatment group received non-invasive ventilation combined with vitamin D. After therapy, the treatment group showed a higher total effective rate compared to the control group. The treatment group exhibited a more pronounced decrease in the partial pressure of carbon dioxide and an increase in the partial pressure of oxygen in arterial blood and arterial oxygen saturation compared with the control group. The levels of forced vital capacity and forced expiratory volume in the first second were higher in the treatment group. Moreover, interleukin-6, C-reactive protein, and procalcitonin levels were lower, while CD3+, CD4+, CD8+, and CD4+/CD8+ levels were higher; quality-of-life scores were lower. Combining non-invasive ventilation with vitamin D can improve blood gas indexes, promote lung function, reduce inflammatory response, and promote immune function in patients with acute exacerbation of chronic obstructive pulmonary disease.