The objective of this study was to estimate the economic costs over the first 2 years of life of Group B Streptococcus (GBS) disease occurring in infants less than 90 days of age. A cost analysis was conducted using a prospective cohort of children born between 2000 and 2003 in the Greater London, Oxford, Portsmouth and Bristol areas of England. Unit costs were applied to estimates of the health and social resource use made by 138 infants diagnosed with GBS disease and 305 non-GBS controls matched for birth weight and hospital stay and time of birth. The health and social care costs for infants exposed to GBS disease were analysed in a multiple linear regression model. The mean health and social care cost over the first 2 years of life was estimated at pound11,968.9 for infants with GBS, compared to pound6,260.7 for the non-GBS controls; a mean cost difference of pound5,708.1 (bootstrap 95% CI pound2,977.1, pound8,391.2, P=0.03). After adjusting for gestational age and other potential confounders in a multiple linear regression, mean societal costs was pound6,144.7 higher among GBS cases than among non-GBS controls (P<0.001). This study shows that the health and social care costs for infants with GBS disease is, on average, two-fold higher during the first 2 years of life than for infants without GBS disease. These data should be used to inform policy decisions regarding the cost-effectiveness of prevention and treatment strategies for GBS disease during early childhood.