Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the β-MSH and β-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits. Display omitted •A POMC mutation is common in the obesity-prone Labrador retriever breed of dog•It disrupts β-MSH and β-endorphin production, both implicated in energy homeostasis•Mutation is absent from other breeds except related flat-coat retrievers•The mutation is associated with weight, adiposity, and food motivation in both breeds Companion dogs from the obesity-prone Labrador retriever breed were found to carry a mutation in POMC in this study by Raffan et al. The mutation is predicted to disrupt production of the neuroactive peptides β-MSH and β-endorphin and was associated with greater weight, adiposity, and food motivation in affected dogs.