Objectives: Cognitive impairment is present in up to 65% of Relapsing Remitting Multiple sclerosis (RRMS) patients and can be extremely debilitating. Although deficits in episodic memory and processing speed occur more frequently than executive deficits, executive dysfunction tends to have a significant impact on MS patients' ability to generate strategies, think divergently, solve and estimate problems, and reason in abstract terms with substantial negative impacts on activities of daily living. In the present study we investigated perfusion detection rate and pattern, as well as the association between perfusion rates and cognitive dysfunction in cognitively impaired RRMS patients., Methods: We present findings from 17 cognitively impaired RRMS patients who were evaluated with a comprehensive neuropsychological battery and additionally evaluated by brain perfusion radiopharmaceutical technetium-99m hexamethyl-propylene amine oxime ( 99m Tc HMPAO)., Results: RRMS patients had hypoperfusion in several predefined Brodmann areas and lobes of the brain, relatively to demographically matched healthy controls according to an established normative database NeuroGam™. However, we noted blood flow reduction, mainly in the frontal lobes and other related prefrontal areas, involving both hemispheres, but with asymmetric left hemisphere predominance. Moreover, associations between measures of response inhibition, set shifting (executive functions) and severity of hypoperfusion in the left frontal lobes were also established., Conclusion: Cerebral hypoperfusion is an integral feature of MS pathology. Executive dysfunction is associated with robust cerebral perfusion deficits in the frontal and prefrontal cortex of cognitively impaired RRMS patients.