Objectives The aim of this blinded, nested case-control study was to compare cats with and without early owner-reported mobility changes using subjective and objective outcome measures (owner-completed questionnaires, orthopaedic examination). Methods A total of 57 cats with and without early owner-reported signs of impaired mobility were allocated to the case (n = 30) and control (n = 27) groups, respectively. Participating owners completed one inclusion and two pre-visit questionnaires (Feline Musculoskeletal Pain Index, VetMetrica). Cats were then visited in their own homes, where they underwent an orthopaedic examination, an assessment of their body condition score and temperament, and the placement of an accelerometer on their collar for 2 weeks. Results There was no significant difference between groups for age category, breed, sex, temperament and body condition score. Case cats scored significantly lower for the Feline Musculoskeletal Pain Index ( P = 0.003) and the VetMetrica domain of Comfort ( P = 0.002), but not Vitality ( P = 0.009) or Emotional Wellbeing ( P = 0.018). Total pain ( P <0.0001), crepitus ( P = 0.002) and thickening ( P = 0.003) scores were higher in case cats, as was the presence of bilateral disease ( P = 0.005, odds ratio 14) and the number of bilaterally affected joints ( P = 0.001). Conclusions and relevance Both the Feline Musculoskeletal Pain Index and orthopaedic examination were able to differentiate cats with early owner-reported signs of impaired mobility from healthy cats. VetMetrica Comfort domain scores indicated a compromised quality of life for cats with early owner-reported signs of impaired mobility compared with healthy cats. Being able to recognise signs of mobility impairment earlier would allow interventions aimed at slowing disease progression, thereby improving feline health and welfare.