Growth hormone (GH) changes body composition, including increasing body water. GH is known to have an anti-natriuretic effect in the kidney, but little is known of its effect on arginine-vasopressin (AVP) release. We studied the effect of GH on AVP release by measurement of copeptin, a fragment from the same precursor protein, in GH-treated patients with GH deficiency. The study was designed as a retrospective cohort study of biobank samples from 34 patients substituted with GH between 1999 and 2004. Copeptin and insulin-like growth factor 1 (IGF-1) results were compared with previously obtained data. An increase in IGF-1 and copeptin was seen at 3 and 6 months’ treatment compared to baseline. Between the 3 and 6 months follow up, copeptin levels were stable. There was a difference in HbA1c between 3 and 6 months (p < 0.01) and between baseline and 6 months (p = 0.042), with higher levels at 6 months. In addition, LDL levels were lower at the 6 months follow up (p = 0.046). The waist circumference at 3 months was lower (p = 0.02). To conclude, three months of GH treatment increased the levels of copeptin and the increase remained at 6 months. This could be a compensatory mechanism balancing the anti-natriuretic effect of GH treatment seen in previous studies.