Background The NHS is the biggest employer in the UK. Depression and anxiety are common reasons for sickness absence among staff. Evidence suggests that an intervention based on a case management model using a biopsychosocial approach could be cost-effective and lead to earlier return to work for staff with common mental health disorders. Objective The objective was to assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of an early occupational health referral and case management intervention to facilitate the return to work of NHS staff on sick leave with any common mental health disorder (e.g. depression or anxiety). Design A multicentre mixed-methods feasibility study with embedded process evaluation and economic analyses. The study comprised an updated systematic review, survey of care as usual, and development of an intervention in consultation with key stakeholders. Although this was not a randomised controlled trial, the study design comprised two arms where participants received either the intervention or care as usual. Participants Participants were NHS staff on sick leave for 7 or more consecutive days but less than 90 consecutive days, with a common mental health disorder. Intervention The intervention involved early referral to occupational health combined with standardised work-focused case management. Control/comparator Participants in the control arm received care as usual. Primary outcome The primary outcome was the feasibility and acceptability of the intervention, study processes (including methods of recruiting participants) and data collection tools to measure return to work, episodes of sickness absence, workability (a worker’s functional ability to perform their job), occupational functioning, symptomatology and cost-effectiveness proposed for use in a main trial. Results Forty articles and two guidelines were included in an updated systematic review. A total of 49 of the 126 (39%) occupational health providers who were approached participated in a national survey of care as usual. Selected multidisciplinary stakeholders contributed to the development of the work-focused case management intervention (including a training workshop). Six NHS trusts (occupational health departments) agreed to take part in the study, although one trust withdrew prior to participant recruitment, citing staff shortages. At mixed intervention sites, participants were sequentially allocated to each arm, where possible. Approximately 1938 (3.9%) NHS staff from the participating sites were on sick leave with a common mental health disorder during the study period. Forty-two sick-listed NHS staff were screened for eligibility on receipt of occupational health management referrals. Twenty-four (57%) participants were consented: 11 (46%) received the case management intervention and 13 (54%) received care as usual. Follow-up data were collected from 11 out of 24 (46%) participants at 3 months and 10 out of 24 (42%) participants at 6 months. The case management intervention and case manager training were found to be acceptable and inexpensive to deliver. Possible contamination issues are likely in a future trial if participants are individually randomised at mixed intervention sites. Harms No adverse events were reported. Limitations The method of identification and recruitment of eligible sick-listed staff was ineffective in practice because uptake of referral to occupational health was low, but a new targeted method has been devised. Conclusion All study questions were addressed. Difficulties raising organisational awareness of the study coupled with a lack of change in occupational health referral practices by line managers affected the identification and recruitment of participants. Strategies to overcome these barriers in a main trial were identified. The case management intervention was fit for purpose and acceptable to deliver in the NHS. Trial registration Current Controlled Trials ISRCTN14621901. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 12. See the NIHR Journals Library website for further project information.