Introduction: During apheresis, anticoagulation is accomplished by use of acid citrate dextrose (ACD). Acid citrate dextrose returns to the donor with the remainder of blood after separation of the targeted blood component. Objectives: This study was conducted to assess the potential toxic effects of ACD in first-time blood donors through clinical and biochemical assessment. Methodology: Seventy -five healthy plateletpheresis donors were recruited in the study where they were subjected to clinical and laboratory assessment just before the procedure (baseline), at 30 min. & at 60 min. during the procedure and 30 min. post procedure. Clinical evaluation included vital signs evaluation and reporting of any clinical manifestation developed. Biochemical assessment included ABG, serum ionized Ca (iCa), ionized Mg (iMg) and parathyroid hormone (PTH) levels. Also activity of erythrocyte phosphofructokinase (PFK) and hematological parameters including RBCs (million/ul), hemoglobin level (Hb g/dl) and hematocrite (Hct %) were evaluated. Results: Apheresis using citrate anticoagulant resulted in changes in mineral homeostasis in the form of hypocalcemia and hypomagnesemia with subsequent tremors (9.3%) and tetany (5.3%). Also, some of the donors exhibited tachycardia and hypotension. Parathyroid hormone (PTH) level increased during apheresis which nearly returned to normal level 30 min. after the procedure while, no significant changes in ABG were detected at different time intervals of the procedure. When RBCs PFK activity was measured, a significant decrease was found during the procedure with significant decrease in RBCs at 60 min. and post 30 min. But no significant changes were detected as regard Hb level and Hct % in comparison to baseline ones. Conclusion: Citrate toxicity may occur even with first time exposure in platelet apheresis donors in form of possible developing tremors, tetany, tachycardia and hypotension with decreased calcium & magnesium levels, increased PTH, decreased erythrocyte PFK activity with subsequent decreased RBCs integrity and possible hemolysis.