Arsenic toxicity is a current global concern due to its devastating toxic effects on human health. Over several millions of people are exposed to this element on daily basis, mainly through drinking water and agricultural pesticides, especially along the Indo-Bangladesh border. Numerous studies have often reflected on arsenic’s deleterious effects on different organs and tissues, including the hematopoietic system. Healthy hematopoiesis is crucial for the homeostasis of functional mature blood cells which are constantly maintained by the bone marrow stem/progenitor cell (HSPC) population. The present study is aimed to understand the hematopoietic cellular status and turnover with special focus on apoptosis and associated alterations in HSPCs in the event of arsenic trioxide exposure in experimental swiss albino mice. The study involves exposure of Swiss albino mice to 10 μg arsenic trioxide/gram of body weight through oral gavage and 5 μg of arsenic trioxide/gram body weight through intraperitoneal injections for a duration of 30 days. The dysregulation in the hematopoietic system was characterized by bone marrow cytochemical analysis, in vitro cellular kinetics study, flow cytometry analysis of hematopoietic populations and component distribution and finally by the apoptosis profile. Upon examination, reduced body weight and reduction in myelopeoxidase (MPO) in the bone marrow cells of arsenic exposed mice were noticed. The diminution in the cell viability supported by apoptosis profile hinted towards hindered hematopoiesis. The in vitro cell culture depicted the catastrophic condition in the hematopoietic compartment of arsenic exposed mice. The flowcytometric analysis revealed the changes in granular population and depletion in CD150 + and Tie2 + HSPCs which confirms deregulation in the bone marrow hematopoietic compartment of the arsenic trioxide exposed mice groups. The study presented an overall as well as hematopoiesis specific scenario of arsenic toxicity that would be beneficial for the development of more awareness regarding this common and prevalent hazardous exposure which severely damages the HSPC population, leading to apoptosis and perturbed mature cellular turnover.