Background Ketamine is a dissociative anesthetic with analgesic properties. Ketamine’s analgesic properties have been suggested to result from its dissociative properties. To our knowledge, this postulate is unsubstantiated. We hypothesize that the dissociative and analgesic properties of ketamine are independent. Methods We conducted a single-site, open-label study of ketamine anesthesia (2mg/kg) in 15 healthy subjects. Midazolam was administered at a pre-specified time point to attenuate dissociation. We longitudinally assessed pre-calibrated cuff pain intensity and quality using Patient-Reported Outcomes Measurement Information System questionnaires, and dissociation, using the Clinician Administered Dissociative States Scale. Mixed effects models were used to assess whether dissociation accounted for the effect of ketamine on pain intensity and quality. Results The dissociation model demonstrated an inverted “U” shaped quadratic relationship between time and dissociation scores. Additive to this effect, midazolam reduced the dissociation adjusted means by 10.3 [95%CI: 3.4 to 17.1] points (p = 0.005). The pain intensity model also demonstrated a “U” shaped quadratic relationship between time and pain intensity. When the pain intensity model was reanalyzed with dissociation scores as an additional covariate, the dissociation term was not retained in the model, and the other effects were preserved in direction and strength. This result was conserved for nociceptive and neuropathic pain quality. Conclusion Ketamine’s analgesic properties are not exclusively caused by dissociation. Thus, ketamine may be used as a probe to advance our knowledge of dissociation independent neural circuits that encode pain. Clinical Trial Number: NCT03553758