Aim: Granulocyte differentiation factor 15 (GDF15) is a growth factor and biomarker for many disorders where Ischaemia Reperfusion Injury (IRI) is pathophysiologically relevant. Hence the need to evaluate GDF-15 as a biomarker in Sickle Cell Disease (SCD). Study Design: This is a cross sectional study. Place and Duration of Study: Department of Haematology, Nnamdi University Teaching Hospital, Nnewi, Anambra state, Nigeria, between January and December 2018. Methods: Ninety subjects were randomly recruited with haemoglobin (Hb) phenotypes SS (test), AS and AA (controls); numbering 30, 28 and 32 respectively. Disease severity was determined by calculating an objective score. 5 mls of blood was collected and used to determine Full Blood Count (FBC), haemoglobin Phenotype and GDF-15 levels (by Enzyme Linked Immunosorbent assay).  Data collected was analysed using Statistical Package for Social Sciences software version 20 (SPSS Inc., IL, Chicago, USA). P< 0.05 was considered as significant. Results: GDF-15 level was found to be significantly different in the different HB phenotypes p= 0.005 and correlated negatively with sickle cell disease severity (r= -0.307, p= 0.098). The difference between median GDF-15 levels of HBSS subjects with mild and moderate disease was statistically significant at p= 0.01. Conclusion: We hypothesize that GDF-15 may be a potential therapeutic target for intervention against ischaemia/reperfusion induced micro- vascular injury.  Natural GDF-15 mimetics may be useful in taking advantage of this potential therapeutic target.