Post-Operative Hyperalgesia (POH) is an uncommon painful condition suffered after surgery. It is poorly identified and usually needs a large dose of strong opioids administration to attenuate pain. Primarily POH originated from the activation of N-Methyl-DE Aspartate Receptor (NMDAR) located at the spinal cord. Hence NMDAR antagonist (ketamine) may inhibit this pain mechanism leading to desirable post-operative pain relief. We presented a case report on how to recognize POH, initiated ketamine infusion, and its limitation. We found ketamine therapy reduced opioid requirements and drastically improve patient daily bed activities.