Depression and anxiety are the most prevalent mental health difficulties in the workplace in the EU, causing immense suffering and costing the global economy €1 trillion each year in lost productivity. Certain sectors, in particular construction, health and ICT, have an elevated risk of mental health difficulties, with those working in Small and Medium Enterprises (SMEs) being particularly vulnerable. However, most SMEs have limited capacity to address mental health promotion and provide mental health interventions to staff. As SMEs comprise more than 90% of all EU businesses, there is a huge potential to influence population health. MENTUPP aims to improve mental health and wellbeing in the workplace by developing, implementing and evaluating a comprehensive, multilevel intervention targeting both clinical (depressive, anxiety disorders) and non-clinical (stress, burnout, wellbeing, depressive symptoms) mental health issues, as well as combating the stigma of mental (ill-) health. The intervention will be tailored for SMEs in construction, healthcare and ICT and assessed in a multi-country Cluster Randomised Controlled Trial. The primary aim is to improve mental health in the workplace, with a secondary aim to reduce depression and suicidal behaviour. MENTUPP will be conducted by an interdisciplinary consortium that includes world leading experts in mental health in occupational settings, depression, anxiety, stress, suicide prevention and stigma. It builds on a solid foundation of evidence, in particular leveraging partner European Alliance Against Depression’s four-level intervention to improve mental health and reduce suicide risk and partner Mates in Construction’s successful workplace intervention to reduce suicide in construction workers. Long-lasting impact is also a key priority of the project, with activities dedicated to the development of replication materials to support long-term use of the MENTUPP intervention in SMEs across Europe.