Study design: Retrospective review. Objective: To evaluate mental health influence on minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) patients. Summary of background data: Poor mental health has been postulated to indicate inferior patient perceptions of surgical outcomes in spine literature. Few studies have assessed mental health as a dynamic metric throughout the perioperative period. Methods: A single-surgeon database was retrospectively searched for patients who underwent primary, elective MIS-TLIF for degenerative or isthmic spondylolisthesis. Summative depressive burden (SDB) was defined by the sum of preoperative and 6-week postoperative 9-item Patient Health Questionnaire (PHQ-9), with Lesser Burden (LB, SDB<10) and Greater Burden (GB, SDB >= 10) cohorts. Patient-reported outcomes measures (PROMs) were compared preoperatively, at 6 weeks, and at final postoperative follow-up (11.4 +/- 10.9 mo), using Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Oswestry disability index (ODI), visual analog scale-back (VAS-B), VAS-leg (VAS-L), and PHQ-9. Improvements at 6-week (triangle PROM-6W), final follow-up (triangle PROM-FF), and minimum clinically important difference (MCID) achievement were compared. Results: The GB cohort consisted of 44 of 105 patients. Demographic variations included older age, higher Charlson comorbidity index, increased hypertension prevalence, and private insurance in the LB cohort ( P <= 0.018). The LB cohort demonstrated better baseline and 6-week PROMIS-PF/ODI/VAS-L ( P <= 0.032) and better final PROMIS-PF/ODI/VAS-L/PHQ-9 ( P <= 0.031). Both cohorts improved in all PROMs at 6 weeks and final follow-up ( P <= 0.029), except for PROMIS-PF at 6 weeks in the GB cohort. triangle PROM-6W, triangle PROM-FF, and MCID achievement rate for PHQ-9 were greater in the GB cohort ( P <= 0.001). Conclusion: On average, patients undergoing MIS-TLIF for degenerative or isthmic spondylolisthesis improved in all PROMs by final follow-up. Patients with GB suffered inferior perceptions of physical function, disability, and leg pain. MCID rates in mental health were higher for GB cohort. Surgeons are encouraged to adopt a compassionate understanding of depressive burden and educate the patient on possible consequential postoperative outcomes.