In 2011, human coxsackievirus B5 (CVB5) caused an outbreak of viral encephalitis in Henan, China. Complete genome sequence analysis based on two isolates showed that the 5' half of the genome (nt 1-4540) had high similarity (>97 %) to that of CVB5 strain GU376747, and the 3' half (nt 4700-7402) showed high similarity (>96 %) to that of human coxsackievirus B3 (CVB3) strain GQ141875. These isolates had the highest similarity (97.7 %) to the Changchun strain, based on the complete genome, rather than to other CVB5 strains isolated from Henan in recent years. There were therefore at least two groups of CVB5 circulating in Henan Province, which evolved at different rates.