Background: Children attending group day-care have an increased risk for infectious diseases. Entry between the age of two and three years could be a “window of vulnerability” where children can strengthen their immune system due to early exposure, but to date there is little or no research on the potential psychological implications of long-term exposure to infectious diseases in group day-care. Objectives: To determine if there is a decline in severity and frequency over time of common infectious diseases in group day-care and whether infectious diseases can be associated with emotional adjustment. By this, it is possible that young children with infectious diseases could show more irritability as they have more difficulties explaining pain. Method: A 4-year population-based cohort study based on data from “The Matter of the First Friendship”. Participants (N = 596) were recruited from group day-care in a rural area in Norway. Parents answered questions each year about their child, family and day-care that included the Strengths and Difficulties Questionnaire (SDQ). Results: Linear regressions showed that overall frequency and severity of infectious diseases in group day-care decline over a 4-year period. Correlation analysis did not find infectious diseases in group day-care to be associated with emotional difficulties in the fourth year. Conclusion: This study supports the suggestion that early exposure to infectious diseases strengthens the immune system and does not have a negative effect on emotional adjustment.