Background Our aim was to determine whether early chronic methicillin-susceptible Staphylococcus aureus (MSSA) colonization in children with cystic fibrosis (CF) is associated at 8 years of age with poorer lung function, poorer nutritional status, and increased exacerbation frequency. Methods In this retrospective cohort study, a total of 52 children with chronic MSSA colonization were included. Of them, 26 were chronically colonized with MSSA before the age of 4 years (early onset), and 26 were chronically colonized from 4 years to 6 years of age (late-onset). At the age of 8 years, lung function, body mass index (BMI) as an indicator of nutritional status and frequency of pulmonary exacerbations were compared between two groups. Results At 8 years of age, BMI was similar between the early-onset and late-onset groups (15.0 [min-max: 12.9-26.8] vs. 15.7 (min-max: 13.0-24.9), p = 0.327]. Percentage of forced expiratory volume in 1 s (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) in 8-year-old children were significantly lower in the early onset group compared to the late-onset group (98 [min-max: 44-139] vs. 106.5 [min-max: 82-131], p = 0.047; 84.9 +/- 25.5 vs. -102.3 +/- 26.3, respectively; p = 0.019], although the percentage of forced vital capacity did not differ significantly between two groups (93.5 [min-max: 45-131] vs. 103 [min-max: 84-119], respectively; p = 0.092). Exacerbation frequency between the ages of 6 and 8 years in the early onset group was higher compared to the late-onset group according to the Poisson regression model [1 (min-max:0-10) vs 0 (min-max:0-4), respectively; p = 0.044]. Conclusions Early chronic MSSA colonization is associated with poorer lung function and frequent exacerbations in children with CF. However, further studies are needed to reveal the cause-and-effect relationship between early chronic MSSA colonization and pulmonary outcome.