Objectives: The assessment of health-related quality of life (HRQoL) is becoming increasingly important in companion animals. This study describes a systematic review and development of a proposed conceptual framework to assess HRQoL in cats with osteoarthritis (OA).Methods: The conceptual framework was developed according to published guidelines. A comprehensive search of the CAB Direct, Scopus, PubMed, and Web of Science databases was carried out for publications in English from inception to November 12, 2019. Search words used were “cat”, “feline”, “chronic pain”, “pain”, and “quality of life”. Publications were selected if they were full-text and peer-reviewed, based on primary data, and identified or measured behavioral symptoms of chronic musculoskeletal pain in cats. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A data extraction form was developed from categories identified in the literature review and piloted on a small number of studies to ascertain the appropriateness for relevant data extraction. Categories were then finalized, and key domains were identified. The domains were then synthesized to develop a conceptual framework.Results: A total of 454 studies were identified, of which 14 met the eligibility criteria and were included in the meta-synthesis. All 14 were assessed to be of good quality. Seven domains related to HRQoL in cats with OA were thematically identified from the data: mobility, physical appearance, energy and vitality, mood, pain expression, sociability, and physical and mental wellbeing. The three main HRQoL domains were pain expression, mobility, and physical and mental wellbeing, which impacted all the others. Pain and mobility impacted all six other domains, with increased pain and decreased mobility negatively impacting physical appearance, energy and vitality, mood, sociability, and physical and mental wellbeing.Conclusions and Relevance: This is the first study to develop an evidence-based conceptual framework for the assessment of HRQoL in cats with OA. The proposed conceptual framework suggests that effective management of chronic pain in cats may improve their overall HRQoL.