Introduction: Psychotropic drug intoxication may require urgent management. Hemoadsorption (HA) may detoxify blood in such cases, but its effect has not been quantified. Methods: We studied in vivo removal of valproate, quetiapine, and escitalopram with HA using the Jafron HA380 cartridge in six sheep. We measured the removal ratio (RR) and clearance (CL) of each agent over time. Results: Mean sorbent-based valproate RR was initially 55.8% (CL: 58.2 mL/min) but declined to negligible levels at 120 min. The mean initial RR for quetiapine was >90% and remained high (72%) at 4 h with CL of 87.2 mL/min at 10 min and 68.7 mL/min at 240 min. The mean RR of escitalopram exceeded 90% at 10 min and decreased to 66.9% at 4 h. The mean CL was 88.0 mL/min at 10 min and 63.2 mL/min at 240 min. Conclusion: HA with the HA380 cartridge achieves effective removal of valproate, quetiapine, and escitalopram. For valproate, adsorptive performance progressively declined over the 4-h treatment period. In contrast, for quetiapine and escitalopram, the function remained substantial for up to 4 h. Further research is required to optimize HA strategies for these drugs and facilitate clinical translation of HA-based blood detoxification.