Background: A link between major depressive disorder (MDD) and haematological as well as co-agulation disorders has been postulated. This study aims to evaluate haematological and haemostatic changes among Nigerians with major depressive disorder Methods: Two hundred volunteers consisting of an equal number of individuals diagnosed with major depressive disorder (MDD) based on DMS-IV criteria and apparently healthy control participated in this study. The blood sample was collected into tri-sodium citrate K2EDTA bottles respectively and was evaluated for some haemostatic parameters , using ELISA, Clauss, Quick’s One Stage, Proctor and Rapaport’s methods. Results: The mean WBC, hemoglobin and differential lymphocyte were significantly higher among MDD total volunteers (p < 0.001). The red cell indices and platelet count were lower among MDD (p <0.001). Also the prothrombin time (PT), fibrinogen, protein-C and erythrocytes sedimentation rate (ESR) were all raised (p <0.001) among volunteers with MDD. Positive associations existed be-tween MCV and RBC (r: 0.364; p<0.001), PT and APTT (r: 0.319 p <0.001), APTT and fibrinogen (r: 0.239, p = 0.017) as well as PT and fibrinogen (r: 0.275 p = 0.006) at 95% confidence interval. Conclusion: Changes in total leucocytes count, lymphocytes values and haemostatic parameters among volunteers with depression may impacts deleterious effects on the immune response as well as haemostatic homeostasis, while decreased red cell indices may suggest occult nutritional anaemia.