Determining suitable copper parameters for monitoring Wilson disease remains a topic of ongoing discussion. International recommendations currently rely on the combination of urinary copper excretion and non-specific liver markers when considering therapy and time elapsed since diagnosis. The emergence of exchangeable copper (CuEX) as a novel measurement reflecting the "free copper pool" held promise as a valuable target to ensure metabolic stability during follow-up, although validation of target ranges remain unknown. We aimed at evaluating CuEX quantification in repeated samples from 92 real-world WD patients during a 2-year period. Patients were classified as "stable" if diagnosis had been made more than one year before and were compliant to stable anti-copper drug and dose. Otherwise, patients were classified as "non-stable". Two-hundred and thirteen CuEX samples were obtained per clinical practice. Overall, 57% of CuEX measurements fell below the reference "range of normality", whereas only 34% were within and 9% were above normal levels. There was no association of CuEX levels with therapy, elapsed time from diagnosis or clinical stability, although most of the samples above normality corresponded to non-stable patients. Only 23.4% of the CuEX samples were aligned with data obtained from concomitant urinary copper excretion. Our findings suggest that CuEX is a suboptimal tool for assessing copper homeostasis when used alone and should be used with caution if no additional information is available. Normal reference intervals for WD-treated patients should be redefined, as most of CuEX quantifications fell in the lower range, with no sign of overtreatment in these patients.