Introduction The American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) 2014 lumbar fusion guidelines for stenosis with degenerative spondylolisthesis (DS) support surgical decompression and fusion as an effective treatment option for symptomatic stenosis associated with DS. The association between the number of levels decompressed in patients with single-level fusion and clinical outcomes has never been published. Methods A retrospective analysis of a single-center, prospectively collected database was performed on 77 patients to compare the effect of the number of decompression levels in patients that received single-level fusion surgery. A total of 77 patients met the criteria. Group one had one level decompressed, group two had two levels decompressed, and group three had three or four levels decompressed. All patients received lumbar fusion surgery at a single spinal level. Outcomes at six months included: Substantial Clinical Benefit (SCB) (ΔODI ≥ 10 points); Minimal Clinically Important Difference (MCID) (ΔODI ≥ 5); no MCID (ΔODI <5 points). Student's t-tests, one-way analysis of variance (ANOVA), and post hoc comparison using unpaired two-tailed student's t-test with Holm-Bonferroni correction were performed. p -values were ranked from smallest to largest, and alpha level adjustments were made. Results A sub-analysis of each group’s clinical outcomes showed that patients with two levels decompressed reached greater clinical outcomes. SCB was obtained by approximately 60% (group one: 12.5% vs. group three: 40%) of the patients. A total of 77.6% (38/49) achieved MCID (group one: 62.5% vs. group three: 55%). Single-level fused patients with two levels of decompression showed an improvement of 48% from baseline ODI, as opposed to group one: 17.85% and group three: 21.1%. Patients belonging to group two showed the lowest rate of no improvement. Baseline ODI scores were similar upon presentation (p=0.46), and the difference was found among groups after six months of follow-up (p=0.009). Post hoc comparison showed statistical significance in the comparison between group two and group three (p=0.009, alpha value: 0.017). Conclusion The addition of more than two levels of decompression to single-level fused patients might be associated with poor clinical outcomes and spinal instability.