Objective To Explore the predictive value and "dose-effect" relationship of serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CRP/ALB) in patients with chronic obstructive pulmonary disease (COPD) for frequent acute exacerbations. Methods A total of 153 patients with COPD in our hospital from July 2021 to July 2022 were selected and followed up for 1 year. According to the acute exacerbation of the patients, they were divided into stable group (n=55), acute plus recombination (n=39), frequent acute plus recombination (n=59), and 51 healthy subjects were selected as control group during the same period. Blood levels of NLR and CRP/ALB were compared among the four groups. Multivariate COX regression analysis was performed to analyze the influencing factors of frequent acute exacerbations in COPD patients, and receiver operating characteristic curve (ROC curve) was used to analyze the value of blood NLR and CRP/ALB levels in evaluating frequent acute exacerbations in COPD patients. The "dose effect" relationship between blood levels of NLR, CRP/ALB and frequent acute exacerbations in COPD patients was analyzed with restricted cubic spline diagram. Results The levels of NLR and CRP/ALB in the blood increase in turn in the control group, stable group, acute exacerbation group, and frequent acute exacerbation group (P＜0.05). NLR, CRP/ALB were independent risk factors for frequent acute exacerbations in COPD patients, and long-term home oxygen therapy was independent protective factor for frequent acute exacerbations in COPD patients (P＜0.05). The AUC value of frequent acute exacerbations in COPD patients assessed by NLR and CRP/ALB combined was 0.849, which was higher than that assessed by NLR (Z statistic=2.924, P=0.004) and CRP/ALB (Z statistic=2.736, P=0.006) alone. NLR (χ2=20.730, P＜0.001), CRP/ALB (χ2=19.931, P＜0.001) had a nonlinear"dose-effect" relationship with frequent acute exacerbations in COPD patients. Both curves were roughly "J" shaped. When NLR＞4.50 and CRP/ALB ＞3.40, NLR (β=0.893, 95%CI=1.389-4.294, P＜0.001), CRP/ALB (β=0.973, 95%CI= 1.451-4.826, P＜0.001) were positively correlated with the risk of frequent acute exacerbations in COPD patients. Conclusion Blood levels of NLR and CRP/ALB in COPD patients are closely related to frequent acute exacerbations, and there is an independent "dose-effect" relationship, which can provide references for clinical assessment of the risk of frequent acute exacerbations