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Background: Psoriasis itself, as well as its immunomodulatory drugs, may alter the immune system, increasing the risk of infections. Recent research has indicated that patients with psoriasis are at an increased risk of developing severe infections including tuberculosis. Objectives: To evaluate and compare the incidence of serious infectious diseases in Korea between patients with psoriasis and participants without psoriasis regarding each treatment modality. Materials & Methods: This nationwide cohort study utilized claims data based on the National Health Insurance Service between January 2005 and December 2018. Results: In total, 293,073 patients with psoriasis enrolled for the analysis of serious infection and 272,400 patients enrolled for the analysis of tuberculosis. Participants without psoriasis matched by age and sex (1:1 ratio) were also enrolled. For serious infection overall, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.21 (1.20–1.23), 1.23 (1.17–1.28), and 1.33 (1.09–1.63) for the non-systemic, non-biologic systemic, and biologic groups, respectively. For tuberculosis overall, the aHRs were 1.15 (1.10–1.20), 1.32 (1.10–1.57), and 6.72 (4.28–10.56) for the non-systemic, non-biologic systemic, and biologic groups, respectively. Conclusion: This study reveals that the risk of serious infection and tuberculosis in patients with psoriasis was significantly higher than in participants without psoriasis. Moreover, patients with psoriasis who received systemic therapy other than phototherapy had a higher risk of these infections compared to those without psoriasis. Also, biologics appeared to increase the risk of tuberculosis in patients with psoriasis. Dermatologists should consider these potential risks when selecting treatment modalities for psoriasis.