Abstract Background Chronic obstructive pulmonary disease (COPD) frequently coexists with various diseases, yet the causal relationship between COPD and these comorbidities remains ambiguous. As a result, the aim of our study is to elucidate the potential causality between COPD and its common comorbidities. Methods We employed the Mendelian randomization (MR) method to analyze single nucleotide polymorphism (SNP) data of common comorbidities with COPD from FinnGen and Integrative Epidemiology Unit (IEU) databases. Causality was primarily assessed using the inverse variance weighting (IVW) method. Multivariable Mendelian randomization (MVMR) analysis was also conducted to eliminate the interference of smoking-related phenotypes. Sensitivity analysis was conducted to ensure the reliability of our findings. Results Preliminary univariable MR revealed an increased risk of lung squamous cell carcinoma (LUSC) (IVW: OR = 1.757, 95% CI = 1.162–2.657, P = 0.008), chronic kidney disease (CKD) (IVW: OR = 1.193, 95% CI = 1.072–1.326, P