Background: Previous observational research has identified associations between depression and chronic respiratory diseases (CRDs); however, the causality of these associations remains uncertain. Methods: In this investigation, we employed a two-sample Mendelian randomization (MR) approach to evaluate the presence and directionality of a causal relationship between depression and CRDs. To discern the direct effect of depression on CRDs, independent of confounders, we applied multivariable MR (MVMR), adjusting for smoking and alcohol intake. We sourced SNPs associated with depression from the Psychiatric Genomics Consortium and the UK Biobank (n=500,199). Furthermore, genetic correlations with 17 CRDs were derived from the FinnGen Consortium. Results: Utilizing a two-sample Mendelian randomization approach, our study discerned that depression potentially elevates the risk for nine types of CRDs, specifically chronic sinusitis, pharyngitis, bronchitis, pneumonia, chronic obstructive pulmonary disease (COPD), asthma, allergic rhinitis, and obstructive sleep apnea (OSA). Adjustments for smoking factors led to a diminution in the observed causal relationship between depression and these CRDs.Conversely, no causal association was identified between depression and the remaining eight CRDs under investigation. Conclusion: Our Mendelian randomization study provided evidence indicating that genetic susceptibility to depression is linked to increased risks for nine specific outcomes of CRDs. Smoking was identified as a potential mediating factor in several of these associations. Thus, the prevention and early detection of depression are crucial in the comprehensive management of CRDs.