In this paper, an attempt has been made to study sedimentation of a red blood cell (RBC) in a plasma-filled tube numerically. Such behaviors are studied for a healthy and a defective cell which might be created due to human diseases, such as diabetes, sickle-cell anemia, and hereditary spherocytosis. Flow-induced deformation of RBC is obtained using finite-element method (FEM), while flow and fluid–membrane interaction are handled using lattice Boltzmann (LB) and immersed boundary methods (IBMs), respectively. The effects of RBC properties as well as its geometry and orientation on its sedimentation rate are investigated and discussed. The results show that decreasing frontal area of an RBC and/or increasing tube diameter results in a faster settling. Comparison of healthy and diabetic cells reveals that less cell deformability leads to slower settling. The simulation results show that the sicklelike and spherelike RBCs have lower settling velocity as compared with a biconcave discoid cell.