The 2009 pandemic infl uenza A(H1N1) was fi rst detected in Malaysia in May 2009. It quickly spread in the general population and contributed to a number of infl uenza-like illness. The objective of the study is to characterize genetic changes in early Malaysian isolates of mild and severe illness of the novel infl uenza, and to compare sequences of viruses circulating in Malaysia to those in other countries between May to September 2009. Viral isolates of 56 mild cases and 10 severe (intensive care unit or fatal) cases were sequenced for haemagglutinin (HA) and neuraminidase (NA). Genome sequencing of the viral RNA was conducted on 5 isolates (3 were from fatal cases). Highly conserved sequences with few sporadic variations were identifi ed in HA and NA. E374K and D222N were identifi ed in 2 viral isolates from patients with severe illness. Phylogenetic analysis showed close genetic relatedness to the vaccine strain A/California/07/09 and other isolates circulating worldwide during the same period. Sporadic variations were identifi ed in the viral isolates, however a larger sample size is required to make associations with disease severity.