Objectives: With increasing survival rates of children with sickle cell disease (SCD) reaching adulthood, there has been a growing interest in the quality of life and mental health functioning of affected individuals. Positive mental health is recognised as a significant dimension of human health that plays an important role in advancing well-being. This study explored the prevalence of positive mental health and functioning among a sample of Ghanaian adults with SCD. Methods: A quantitative cross-sectional survey design was implemented for data-gathering. A random sample of 62 adult SCD patients (21 to 56 years; mean age of 29 years) receiving treatment at the Sickle Cell Clinic of the Ghana Institute of Clinical Genetics at the Korle-Bu Teaching Hospital completed the Mental Health Continuum–Short Form (MHC-SF). Descriptive statistics and reliability indices were estimated for the MHC-SF. We implemented Keyes’s criteria for the assessment and categorisation of levels of mental health to determine the prevalence of positive mental health and functioning. Results: We found a high level of positive mental health (66% flourishing; 26% moderately mentally healthy; 8% languishing) and functioning, with no significant difference between the genders. A total of 34% of the participants were functioning at suboptimal levels and were at risk of psychopathology. Conclusion: This study gives the first overview of the prevalence of positive mental health and functioning in a clinical population in Ghana. Although the majority of participants were flourishing, contextually appropriate positive psychological interventions are needed to promote the mental health of SCD patients who are functioning at suboptimal levels, which would, inherently, also buffer against psychopathology.