Background: Children with sickle cell disease (SCD) are particularly susceptible to pneumococcal infection. Administration of the 13-valent conjugate pneumococcal vaccine which is now available in Nigeria may help to reduce the incidence. Objectives: To determine the serum level of pneumococcal-specific IgG (PIgG) in a cohort of patients with SCD after administration of a single-dose of a 13-valent pneumococcal conjugate vaccine. Methods: The study was conducted between December 2011 and March 2012 among children with SCD aged 5 months to 5 years attending the sickle cell clinic in five public hospitals in Lagos. Altogether, 151 children with SCD and 52 without it (controls) were recruited by convenience sampling from the sickle cell clinics and well-child clinics. Blood samples were collected for PIgG concentrations before and 2 months after a single dose of the Prevenar 13 vaccine. Seroconversion was defined as a fourfold or greater increase in antibody concentration after vaccination while those with PIgG concentrations ≥200 μU/ml were considered to have protective levels. Results: The age range of the total study group was 5–60 months with a mean (SD) of 39.04 (15.44) months and a median of 39 months. The mean (SD) ages of subjects with and without SCD were 38.91 (15.75) months and 16.39 (15.45) months, respectively. The PIgG concentration 2 months post-vaccination was significantly greater than the pre-vaccination levels in all age categories in both groups and almost all subjects had protective PIgG concentrations 2 months after vaccination. A four-fold increase in PIgG concentration was detected more commonly in the controls than in SCD patients. Conclusion: Prevenar 13 provided protective immunity in all vaccinated children but those under 2 years of age who had non-protective levels pre-vaccination benefited the most. [ABSTRACT FROM AUTHOR]