The present investigation establishes deltamethrin resistance in the common bed bug, Cimex lectularius, populationcollected from New York City (NY-BB). The mortality resistance ratio indicated that NY-BB population was 264-fold more resistant to 1% deltamethrin in contact bioassay compared to one insecticide- susceptible population collected in Florida (FL-BB). Specific enzyme activities (general esterase, glutathione S-transferase, and 7-ethoxycoumarin O-deethylase) of NY-BB were not statistically different from those of FL-BB, indicating that the metabolic factors are not associated with the deltamethrin resistance in NY-BB. Complementary DNA fragments that encoded the open reading frame of voltage-sensitive sodium channel α-subunit genes from the FL-BB and NY-BB were obtained by homology probing PCR and sequenced. Sequence alignment of the internal and 5’ and 3’ RACE fragments generated a 6500 bp cDNA sequence contig, which was composed of a 6084 bp open reading frame (ORF) encoding 2027 amino acid residues and 186 bp 5’ and 230 bp 3’ untranslated regions (5’ and 3’UTRs, respectively). Sequence comparisons of the complete open reading frames of the sodium channel genes identified two point mutations (V419L and L925I) that were presented only in the NY-BB population. L925I, located the intracellular loop between IIS4 and IIS5, has been previously found in the pyrethroid-resistant populations of whitefly (Bemisia tabaci) that was more than 100-fold resistant to fenpropathrin. V419L, located in the IS6 transmembrane segment, is a novel mutation. This evidence suggests that the two mutations are likely the major resistance-causing mutations in the deltamethrin-resistant NY-BB via a knockdown-type nerve insensitivity mechanism.