Serial fluorine 18 fluorodeoxyglucose (18F‐FDG) positron emission tomography–CT (PET/CT) is commonly used in human oncology to prognosticate and evaluate for therapeutic effectiveness. In this pilot study, dogs with naturally occurring appendicular osteosarcoma were evaluated with serial 18F‐FDG PET/CT in an attempt to assess for response to therapy, prognostic factors, and appropriateness of imaging intervals. Fourteen dogs were enrolled in the trial. All dogs had the initial 18F‐FDG PET/CT (PET1), with nine dogs having their end‐of‐therapy 18F‐FDG PET/CT (EoT PET) 3 months after stereotactic body radiation therapy (SBRT) to the primary tumor. The median percent change from the PET1 to the EoT PET for the standard uptake value maximum (SUVmax%) was −58% (range: −17 to −88%), metabolic tumor volume (MTV%) was −99.8% (range: −65 to −100%), and total lesion glycolysis (TLG%) was −99.8% (range: −75 to −100%), all of which were significant (P < .05, <.05, and <.05, respectively). On evaluation, it was found that volumes of GTV and CTV were significant for survival (P < .05 and <.05), MTV1, TLG1, and SUVmax on the EoT PET (SUVmaxEoT) were predictive of metastasis (P < .05), and the SUVmax% was significantly correlated to the time to first event (P < .05). Based on this data, serial 18F‐FDG PET/CT performed 3 months after SBRT can show a significant reduction in avidity, and the quantitative data collected may help predict metastatic disease in canine appendicular osteosarcoma.