<b>Background: </b>Pharmacodynamic studies and data concerning adaptation of thyroid substitution in patients with substituted hypothyroidism during plasma exchange (PE) is not available. <b>Case Report: </b>We measured TSH, fT₃ and fT₄, total T₄, thyroxin binding globulin (TBG), and albumin before and after 5 PE procedures in a 37-year-old women who underwent PE for a therapy-resistant polyneuropathy. Thyroxin was increased empirically by 8% resulting in a dose of 1.95 µg/kg per day. <b>Results: </b>Despite larger reductions of total T₄ and TBG over a series of 5 PEs (40-50% from baseline), only small reductions of 8% in fT₃ and fT₄ concentrations were documented with a concomittant increase in TSH level. Changes of fT₄, fT₃, and TSH remained within normal range. <b>Conclusions: </b>i) Despite a significant decrease in total thyroid hormone pool following PE, fT₄, fT₃, and TSH concentrations changed only slightly. ii) Based on this observation, a general increase in thyroid replacement therapy before PE cannot be recommended, but considered in case of a high normal TSH level.