BACKGROUND: Among non-pharmacological interventions, Multiwave Locked System (MLS) Laser therapy has been used in patients with several musculoskeletal pathologies and in combination with other therapeutical interventions. The effects of sole MLS therapy on pain and function in patients with chronic non-specific low-back pain are unknown. OBJECTIVE: The objective of this study was to investigate the effects of MLS Laser therapy on pain, function, and disability in patients with chronic non-specific low back pain in comparison to a placebo treatment group. METHODS: Forty-five patients were randomized into two groups: the MLS Laser group and the Sham Laser group, undergoing 8 sessions of either a MLS Laser therapy or a Sham Laser therapy, respectively. At the beginning of the therapy (T0), at the end of the therapy (T1), and 1 month after the end of therapy (T2) patients were assessed for low back pain (by means of a VAS scale), function (by means of kinematic and electromyographic assessment of a forward bending movement) and self-reported disability (by means of the Roland-Morris and Oswestry Disability questionnaires). RESULTS: There was a significant reduction of pain and disability in both groups at T1 and T2 in comparison with T0. At T2 patients in the MLS group showed a significantly lower pain in comparison with patients in the Sham group (VAS = 2.2 ± 2 vs. 3.6 ± 2.4; p< 0.05). No differences between the two groups were found for function and disability. CONCLUSION: Both MLS Laser and Sham Laser therapies lead to a significant and comparable reduction in pain and disability in patients with chronic non-specific low back pain. However, one month after treatment, MLS Laser therapy has been found to be significantly more effective in reducing pain as compared to sham treatment.