Background: In patients with major depression, the function of most endocrine axes is altered compared to healthy subjects. The orexigenic hormone ghrelin, which shows higher plasma levels in females than males, interacts with several of these endocrine axes. In addition, ghrelin levels in depressed patients decrease with psychopathological improvement. Therefore, we hypothesized that ghrelin levels in patients with major depression would be higher than in healthy subjects. Methods: Nocturnal (20:00–07:00 h) secretion patterns of ghrelin in 20 patients with major depression [11 females, age 39.4 ± 10.2 years (mean ± standard deviation); 9 males, age 38.3 ± 10.4 years] with a total score on the Hamilton Depression Rating Scale, 21-item version, of 24.8 ± 5.2 and 20 healthy subjects [11 females, age 38.7 ± 10.8 years; 9 males, age 39.1 ± 11.2 years] were determined following an adaptation night. Results: Ghrelin plasma levels of depressed patients and matched healthy subjects did not differ at any point in time when stratified for sex. Accordingly, the area under the curve was comparable: depressed females, 423.3 ± 103.4; healthy females, 398.0 ± 94.6; depressed males, 266.3 ± 56.9, and healthy males, 228.4 ± 41.3. Conclusion: This is the first comparison of ghrelin secretion patterns in patients with major depression and healthy controls. Surprisingly, no relevant differences were ascertained between the two groups.