Abstract: Introductions: Mystical experiences are powerful experiences that may have therapeutic value. Ketamine, a dissociative anesthetic, has shown potential to induce mystical experiences. However, little research has explored this phenomenon, particularly in treatment-resistant depression.Methods: We analyzed clinical data from 60 veterans with treatment-resistant depression receiving a total of 189 ketamine treatments. Veterans either received intranasal esketamine or racemic parenteral ketamine (intravenous or intramuscular). The Revised Mystical Experience Questionnaire (MEQ-30) was administered following ketamine treatments to assess the occurrence of mystical experience. A linear mixed model was used to examine the association between MEQ-30 scores and several treatment-related variables including gender, age, treatment number, dose, comorbid post-traumatic stress disorder, and pretreatment depression rating scores (PHQ-9).Results: Complete mystical experience was reported in 17.02% of esketamine treatments and 18.19% of racemic ketamine treatments. In the esketamine group, a greater number of treatment sessions was associated with higher MEQ-30 scores (p = 0.05). In the racemic ketamine group, higher doses were associated with higher MEQ-30 scores (p = 0.002).Discussion: These findings suggest that ketamine can occasion mystical experiences in veterans with treatment-resistant depression. Future studies should further explore the mystical-type effects of ketamine as a potential contributor to its therapeutic effect in treatment-resistant depression.