Introduction: Vitiligo is an acquired disorder that is recurrent with certain chemokines that were found to play a significant role in its complex pathology. Objective: This study aimed to evaluate carbon dioxide (CO2 )fractional laser efficacy on serum RANTES (regulated upon activation, normal T-cell expressed and secreted) and clinical scoring in vitiligo patients. Case Report: Sixty participants, selected from Kasr Al-Ainy teaching hospital dermatology outpatient clinic, Cairo University from August 2017 till March 2019 were assigned into a control group (A), including 30 age and gender-matched healthy volunteers and a study group (B) including 30 adult stable non-segmental vitiligo patients. All participants in group (A) were exposed to daily sunlight for 3 months, while patients in group (B) received 3 CO2 fractional laser monthly sessions with a wavelength of 10600nm along with sunlight exposure starting on the 5th day after every session for 3 months. Assessment of serum RANTES in all participants was done before and after interventions in both groups and vitiligo area severity index (VASI) score was taken before and after the intervention in all patients of the group (B). Discussion of Results: There was a significant difference (p __ampersandsignlt; .001) in the serum RANTES levels when comparing pre to post-study results in the patients __ampersandsignlsquo;group, while there was no significant difference (p = .72) in serum RANTES levels when comparing pre to post-study results in the control group. For the VASI score, there was a significant difference (p __ampersandsignlt; .001) in scores when comparing pre to post-study results in the patients __ampersandsignlsquo;group. Conclusion: Adding fractional CO2 laser to sun exposure surpasses sun exposure alone in improving stable non-segmental vitiligo patients__ampersandsignrsquo; outcomes.