Background Sickle cell disease (SCD) is a severe genetic blood condition affecting mainly people of black and Mediterranean origin. The disease is associated with serious physical complications and some affected persons have increased social and psychological difficulties. SCD patients have an increased risk of psychiatric co-morbidity compared with the general population. The severity of pain and self-perceived stigma may be risk factors while levels of spirituality/religiosity and social support may be protective against the development of psychiatric co-morbidity, but this had not been sufficiently explored. Aim This study aimed to determine the prevalence, patterns and correlates of psychiatric co-morbidity in adult outpatient attendees of sickle cell disease centre in Benin City, Nigeria. Methods A cross-sectional descriptive study conducted between February and August 2018. Two hundred participants who met the inclusion criteria for the study were selected as study participants using a random sampling method. A semi-structured questionnaire, Mini International Neuropsychiatric Interview (MINI), Oslo Social Support Scale (OSS), Ironson-Woods Spirituality/Religiousness Index (IWSRI) and Measures of Sickle Cell Stigma were utilized for assessing socio-demographic characteristics, psychiatric co-morbidity, social support, spirituality/religiosity and stigma respectively. Results The prevalence of having any psychiatric morbidity was (n=65/200; 32.5%). The commonest psychiatric diagnoses were major depression (n=37/200; 18.5%) and anxiety disorders (n=14/200; 7%). Unadjusted bivariate analysis showed that the participants who were diagnosed with a psychiatric morbidity, were significantly more likely to have poorer social support, have higher mean pain score, higher mean total stigma scores and higher mean scores for all subcategories stigma such as social exclusion, internalized stigma, disclosure concerns and expected discrimination. Also, the mean religiosity, spirituality and combined spirituality and religiosity scores were significantly lower amongst participants with psychiatric co-morbidity. Finally, multivariate analysis revealed that the independent correlates of psychiatric co-morbidity were poor social support (p=0.001), stigma (p=0.002) and spirituality/religiosity (p=0.001). Conclusion Psychiatric morbidity in individuals who are suffering from Sickle Cell Disease is associated with the severity of pain, poor social support, lower levels of spirituality/religiosity and higher level of perceived stigma. This study suggests the need for screening and management of psychological disorders in individuals suffering from Sickle Cell Disease. This may, in turn, improve overall clinical outcome.