Reversible splenial lesion syndrome (RESLES) is rare findings that are described in various etiological conditions. A few recent reports suggested hyponatremia as a potential etiological agent of RESLES. In this report, we illustrate a 46‑year‑old‑male with RESLES who manifested with impairment of consciousness and recovered rapidly after normalization of hyponatremia. We discuss hyponatremia as a factor which might be playing a role either as a primary agent or a contributory one in this manifestation. Besides, we also discuss the possible significance of the other clinical factors including concurrent sinusitis and medication usage in association with RESLES. We think that the detailed illustration of this case may present substantial perspectives regarding the unknown aspects of the pathophysiology of RESLES. The clinical impact and underlying pathogenesis of this entity are warranted to be clarified in future large‑scale studies.