Children with sickle cell disease (SCD) are at high risk of severe infection with Streptococcus pneumoniae (SP). From 2002, all children aged <5 years in the UK with SCD were recommended 7-valent pneumococcal conjugate vaccine (PCV-7) in infancy and 23-valent pneumococcal polysaccharide vaccine boosting, in addition to regular penicillin prophylaxis. Our objective was to determine the nasopharyngeal (NP) carriage rate of SP in children aged <5 years with SCD before and after vaccination with PCV-7 (by vaccine, cross-protection and non-vaccine serotypes). NP swabs were obtained from 63 children attending the Royal London Hospital or Newham General Hospital paediatric haematology clinic between April 2001 and April 2002. Later, NP swabs were obtained from 43 children attending the clinic between June and December 2004 after a PCV-7 vaccination programme. All SP isolated by culture were serotyped and susceptibility to penicillin measured. In the first study group, 13 samples grew SP with 1 sample containing 2 different serotypes, giving a carriage rate of 21%. Four (31%) were intermediately susceptible to penicillin. In the second group overall NP carriage rate had decreased to 9% (n=4), and the proportion directly or indirectly covered by the PCV-7 vaccine fell from 13/14 to 2/4 (P=0.11). One (25%) of these isolates was intermediately susceptible to penicillin. The introduction of PCV-7 appears to be associated with a shift in distribution of serotypes carried by children with SCD. This may have implications for vaccine effectiveness.