Arsenic (As) is a toxic trace element with neurodevelopmental, carcinogenic, and other adverse effects. Meanwhile, selenium (Se) is an antioxidant trace element with essential physiological roles in humans. The preterm neonate is the most heavily transfused patient. The multiple blood transfusions could expose this vulnerable group to trace elements with variable effects. This study aimed to quantify As and Se in various blood products that were used in neonatal blood transfusions alongside an estimate of a dose per transfusion. In addition to exposure quantification, database mining and molecular docking analysis were performed to explore potential detoxification strategies. Samples from transfusion bags: N = 120; 30 samples of each type of blood product (plasma, platelets, packed RBCs (pRBCs), and whole blood “WB”) were analyzed for As and Se by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The As and Se medians of all blood units were 0.6 and 74 μg/L, respectively. About 20% of donors have As levels above 1 μg/L. In addition, 74% of donors have Se levels less than 100 μg/L (the level of sub-optimal activity of the antioxidant enzyme glutathione peroxidase), and 60% of the donors have Se levels below the accepted minimum Se level (80 μg/L). The pRBCs were the units with the highest As and Se content. Meanwhile, WBs were the units with the highest dose per transfusion. Key methyl donors—folic acid, S-adenosylmethionine (SAM), and glutathione (GSH)—showed strong binding affinity to the active site of arsenite methyltransferase (AS3MT), a crucial enzyme in As metabolism. These ligands interacted with conserved catalytic residues such as ASN173, ASP115, and CYS92, suggesting a supportive role in enhancing As methylation and clearance. The present study highlights that neonates are exposed to As and Se via different blood product transfusions with high potential to increase As and decrease Se after transfusion. It is recommended to select donors and screen blood units with optimal Se levels and minimal As content for neonatal transfusions. The integration of in silico docking with exposure assessment adds mechanistic insight and highlights the potential for targeted nutritional interventions to reduce As toxicity in vulnerable neonatal populations.