Abstract: Background: To determine the profile of vitamin D and interleukin-8 (IL-8) in COPD exacerbation. Method: This research is an analytical study with a cross-sectional approach conducted at the Wahidin Sudirohusodo Hospital Makassar from March-June 2020. Serum levels of vitamin D (25-hydroxyvitamin D) and IL-8 were measured using the ELISA method in 65 exacerbated COPD patients based on clinical examination, chest radiograph, & spirometry. The exacerbation criteria were based on Anthonisen and divided into two groups according to the exacerbation frequency in the past year (frequent exacerbations was often ≥ 3 times/year, infrequent exacerbation < 3 times/year) and related to gender, age, nutritional status, smoking status based on the Brinkman index, and obstruction degree according to the Global Initiative for Obstructive Lung Disease (GOLD) 2019. Results: This study consisted of 65 exacerbated COPD subjects (62 men, 95.4%), with age of ≥ 60 years 73.8%, frequent exacerbations of ≥ 3 times/year, 69.3%, vitamin D deficiency status of 76.9 %, and it was found to be significantly lower (15.1 ng/ml) at the frequent exacerbations of ≥ 3 times/year (P <0.01). The means of IL-8 levels were 187.48 +68.30 ng/L and found to be significantly higher (206.7 ng/L) in the frequent exacerbations ≥ 3 times/year (P <0.01). In all subgroups according to gender, age, nutritional status, smoking status, and obstruction degree, there was a tendency for the lowest vitamin D and higher IL-8 in the frequent exacerbations of ≥3times/year. Conclusion: Vitamin D levels were found to be the lowest and IL-8 was higher in COPD patients with frequent exacerbations of ≥ 3 times/year, compared to those with the infrequent exacerbations of < 3 times/year.