Copyright © 2014 by the Endocrine Society. Context: Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated. Objective: The aim of this study was to determine the effect of CSHI on SHS in AD. Setting and Design: This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), GastrointestinalSymptomRating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment. Results: Ten participants completed the study. Baseline SHS scores (mean- SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (±2.4), mental component summary 53.3 (±3.0); GHQ-28 18.1 (±3.3); GSRS 3.7 (±1.6), and AddiQoL 94.7 (±3.7). FS was similar to other AD cohorts 13.5 (±1.0) (P=0.82). UFC between treatments was not different (P=0.87). The salivary cortisol at 0800 h was higher during CSHI (P= 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain. Conclusions: Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not improve SHS in AD with good baseline SHS. This casts some doubt on the potential benefit of circadian cortisol delivery on SHS in AD.