Several schizophrenia brain regions exhibit decreased dysbindin. Dysbindin modulates copper transport crucial for myelination, monoamine metabolism, and cellular homeostasis. Schizophrenia patients (SZP) exhibit increased plasma copper, while copper-decreasing agents produce schizophrenia-like behavioral and pathological abnormalities. Therefore, we sought to determine dysbindin and copper transporter protein expression and copper content in SZP. We studied the copper-rich substantia nigra (SN) using Western blot and inductively-coupled plasma mass spectrometry. We characterized specific protein domains of copper transporters ATP7A, CTR1, ATP7B, and dysbindin isoforms 1A and 1B/C in SZP (n = 15) and matched controls (n = 11), and SN copper content in SZP (n = 14) and matched controls (n = 11). As a preliminary investigation, we compared medicated (ON; n = 11) versus unmedicated SZP (OFF; n = 4). SZP exhibited increased C-terminus, but not N-terminus, ATP7A. SZP expressed less transmembrane CTR1 and dysbindin 1B/C than controls. ON exhibited increased C-terminus ATP7A protein versus controls. OFF exhibited less N-terminus ATP7A protein than controls and ON, suggesting medication-induced rescue of the ATP7A N-terminus. SZP exhibited less SN copper content than controls. These results provide the first evidence of disrupted copper transport in schizophrenia SN that appears to result in a copper-deficient state. Furthermore, copper homeostasis may be modulated by specific dysbindin isoforms and antipsychotic treatment.