Shoulder and neck pain (SNP) and fibromyalgia syndrome (FMS), two musculoskeletal conditions of unknown pathogenesis, share some common features in terms of altered neuroendocrine responses, pain and stress perception. However, the pain distribution in SNP is localized, whereas in FMS is more widespread. Because regional musculoskeletal pain may represent an intermediate stage along a continuum towards widespread musculoskeletal pain we compared the cortisol awakening response (CAR) in women with SNP with the CAR in FMS patients and healthy controls (HC) in a controlled hospital-hotel setting. The aim of the study was to investigate whether SNP is related to a deviant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Eighteen women with SNP, 29 female FMS patients, and 27 female HC participated in the study. Cortisol samples were collected upon awakening, 30 and 60 min later. Questionnaires measuring pain levels, sleeping problems, perceived stress, and psychological characteristics were administered to the participants. Compared with HC, women with SNP had a tendency towards higher cortisol levels, whereas FMS had lower cortisol levels. Adjustment for potential confounders did not influence the results. Women with SNP and FMS patients reported more health complaints, pain, and perceived stress than the HC, but women with SNP were less affected than the FMS patients. Women with SNP showed a tendency towards an elevated HPA axis activity compared with HC. The current findings may indicate that the hypercortisolism in regional musculoskeletal pain represent an intermediate stage towards the development of a hypocortisolism in widespread musculoskeletal pain.