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Abstract Background There is limited knowledge of the long‐term effects on the immune system after treatment for diffuse large B‐cell lymphoma (DLBCL). Methods This study included DLBCL patients from the Danish Lymphoma Registry who obtained complete remission (CR) after (R)‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)‐like immunochemotherapy. Each R+ CHOP‐like treated patient was matched to five comparators from the Danish background population and furthermore compared to R− CHOP‐like treated patients. Incidence rate ratios (IRRs) and risk differences (RDs) were calculated for a wide range of infections, autoimmune conditions, and immune deficiencies (AC‐IDs) combined and by subtypes. Results R+ CHOP‐like treated patients had a higher risk of infections overall (IRR 1.5, 95% confidence interval [CI] 1.4–1.7: 10‐year RD 5.0%, 95% CI 2.2%–7.8%) and for a majority of the subtypes than matched comparators. Likewise, they had a higher risk of AC‐IDs overall (IRR 1.4, 95% CI 1.1–1.7; RD 0.8%, 95% CI 0.7%–2.2%) than matched comparators, however only of clinical relevance for three subtypes; autoimmune diseases of the endocrine system, sarcoidosis and immune deficiencies. The addition of rituximab to CHOP‐like therapy did not alter the incidence rates (IR) of infections overall (IRR 1.1, 95% CI 0.9–1.3) or AC‐IDs overall (IRR 0.8, 95% CI 0.5–1.3) compared to CHOP‐like therapy alone, although the IR for respiratory infections was significantly elevated (IRR 1.5, 95% CI 1.1–2.1). However, an increased use of IVIG treatment was observed among R+ CHOP survivors. Conclusion R‐CHOP‐like treated patients face an increased risk of infections and AC‐IDs overall compared with the background population. The risk of infections and AC‐IDs did not change overall after the addition of rituximab to CHOP, however, an increased risk of respiratory infections is notable. These findings could highlight the need for expanded vigilance and prophylaxis strategies.