Sickle cell disease has many clinical impacts, one such rare finding is systemic hypertension although the literature to support it is debatable. Hypertension along with other key components of sickle cell pathology is one of the reversible causes of posterior reversible encephalopathy syndrome (PRES). Although its triggering factors and pathophysiology is not well documented, hypertension is one of the easily reversible causes of PRES. A well-controlled blood pressure is an aim for reversibility and future recurrence of PRES. However, the addition of other medications like anticonvulsants (levetiracetam and lacosamide) to prevent seizures as a consequence of PRES still remains debatable. Considering the case reported below, the addition of Hydroxyurea to the treatment can be another cause of the recurrence of PRES and needs to be weighed for its risks and benefits.