OBJECTIVE To investigate caregiver burden and its potential associations with psychosocial function and veterinary service use among dog and cat owners and with factors related to treatment plan adherence among owners of animals with chronic or terminal disease. DESIGN Cross-sectional, observational study. SAMPLE 124 clients of a small animal hospital. PROCEDURES Study participants were recruited by email. Owners of sick animals were blindly matched with owners of healthy animals (62/group) by age, gender, and companion animal species. Respondents completed electronic questionnaires related to demographics and previously described measures of caregiver burden, psychosocial function, and treatment plan adherence. Veterinary medical records were reviewed to verify animal health status and assess veterinary service use (billable and nonbillable contacts with veterinary staff) in the 12 months prior to study enrollment. Variables were tested for association by statistical methods. RESULTS Questionnaire scores reflected greater caregiver burden; greater symptoms of depression, anxiety, and stress; and poorer quality of life for respondents with sick animals than for respondents with healthy animals. Greater caregiver burden was associated with scores reflecting poorer psychosocial function and with greater veterinary service use. The number of nonbillable, but not billable, contacts was greater for respondents with high caregiver burden than for those without this finding. Treatment plan factors associated with greater caregiver burden included changes in routine because of the animal's condition and perception that following new rules and routines for management of the condition was challenging. CONCLUSIONS AND CLINICAL RELEVANCE Awareness of potential caregiver burden and psychosocial distress in clients with sick companion animals may help veterinarians identify opportunities for an empathic response. Future research should assess directionality of the relationship between these factors.