The pandemic of obesity is of great concern as its associated co-morbidities are devastating; causing lifelong burden to individual’s health and is economically costly to a country. Factors that lead to obesity are a combination of environmental and genetic factors. The Pro-opiomelanocortin (POMC) gene resides in chromosome 2p23.3, and its protein is composed of 241 amino acids which is responsible for the production of polyhormones that regulate appetite and food intake. The study aimed to investigate the prevalence of the RsaI single nucleotide polymorphism (SNP) site in the 5’-untranslated region (UTR) of POMC and its possible association with obesity among 302 multi-ethnic Malaysian subjects (142 obese, 160 non-obese; 120 males, 182 females) from the Kampar Health Clinic. Subjects were recruited by convenience sampling with informed consent and socio-demographic data as well as anthropometric measurements were taken. Subjects were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from blood. The distribution of the RsaI genotypes was significantly different among the different ethnicities, but the mutated RsaI (- / -) genotype was rare as it only occurred in 8.9% of the subjects. With the frequency of the RsaI (-) allele of 0.31, it was associated with the percentage of skeletal muscles (p