The anesthetic-surgical stress response consists of metabolic, neuroendocrine, hemodynamic, immunological, and behavioral adaptations through chemical mediators such as the adrenocorticotropic hormone, growth hormone, antidiuretic hormone, cortisol, aldosterone, angiotensin II, thyroid-stimulating hormone, thyroxine, triiodothyronine, follicle-stimulating hormone, luteinizing hormone, catecholamines, insulin, interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, and prostaglandin E-2. Behavioral changes include adopting the so-called prayer posture, altered facial expressions, hyporexia or anorexia, drowsiness, sleep disorders, restriction of movement, licking or biting the injured area, and vocalizations. Overall, these changes are essential mechanisms to counteract harmful stimuli. However, if uncontrolled surgical stress persists, recovery time may be prolonged, along with increased susceptibility to infections in the post-operative period. This review discusses the neurobiology and most relevant organic responses to pain and anesthetic-surgical stress in dogs and cats. It highlights the role of stress biomarkers and their influence on autonomous and demeanor aspects and emphasizes the importance of understanding and correlating all factors to provide a more accurate assessment of pain and animal welfare in dogs and cats throughout the surgical process.