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Genetic factors may interact with physical activity levels to modify obesity risk. Our aim was to explore the influence of rs1801260 single-nucleotide polymorphism (SNP) (3111T/C) of CLOCK gene on obesity risk, and to examine its potential interaction with lifestyle factors in an elderly population within the SUN (“Seguimiento Universidad de Navarra”) Project. Subjects (n = 903, aged 69 ± 6 yrs) were recruited from the SUN Project. DNA was obtained from saliva, whereas lifestyle and dietary data were collected by validated self-report questionnaires. Genotype was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) plus allele discrimination. A significant interaction was observed between the 3111T/C SNP of CLOCK gene and sex for overweight/obesity risk ( p for sex × CLOCK interaction <.001). Our results showed that women carrying the C allele of CLOCK gene had a marginally significant lower risk of overweight/obesity compared with noncarrier—TT—subjects (odds ratio [OR]:.61, 95 % confidence interval [CI]:.36