Objective To determine the effect of acute infectious diseases on the cognitive function in the elderly and explore the underlying mechanisms. Methods A 1∶2 matched nested case-control study was carried out retrospectively on 72 hospitalized elderly with coexisting acute infectious diseases and 144 age-matched in-patients without the infection admitted in our hospital from January 2009 to December 2013. All the subjects had annual cognitive tests for 4 consecutive years, which included the Mini-Mental State Examination (MMSE), Word List Recall, Delayed Recall, Animal Category Fluency, and Symbol Digit Modalities tests. The differences in mean cognition scores of the 4 years’ measurement were compared between the 2 groups by multivariable mixed linear models. Results After adjusting for hypertension and body mass index (BMI), the mean MMSE, Word List Recall, Delayed Recall, Animal Category Fluency, and symbol Digit Modalities score of the repeated measurement were significantly lower in the elderly with coexisting acute infectious diseases than those without (all P＜0.05) . Conclusion Cognitive function impairment is more common in the elderly with acute infectious diseases than those without.