The aim of this study was to assess whether long-term administration of hydroxychloroquine (HCQ) is protective from influenza in patients with rheumatoid arthritis and systemic lupus erythematosus. Using a propensity score-matched design, patients who were prescribed HCQ for more than 10 months were matched with patients of the same gender, age group, and Charlson Comorbidity Index score who did not receive HCQ. A logistic regression model was used to estimate the association between the HCQ exposure and influenza after adjusting for covariates. We found no evidence that long-term HCQ exposure can provide a protective effect against influenza during an influenza season.