Climate change is considered as the biggest long-term threat for humanity and is associated with anthropogenic greenhouse gas emissions (GHG) released into the atmosphere. In line with the Climate Change Act 2008, the NHS Carbon Reduction Strategy requires reduction of its GHG emissions by 50% by 2025, 64% by 2030 and 80% by 2050 from 1990 levels. In addition, recent Government pledges refer to net-zero carbon for UK buildings by 2050, which requires further GHG reduction in the future. Climate change related temperature increases are expected to reduce building heating demand and increase building cooling demand, while climate change related legislation requires the decarbonisation of building energy sources. Hospital sites consist of multiple individual buildings built over the last century, multiple scattered heating and cooling plants, many electrical substations â presenting difficulties in both the energy monitoring and management of hospital buildings. These challenges make the transition to net-zero particularly difficult for hospitals compared to other buildings. This study has been designed to monitor internal conditions, heating and cooling energy demand, and annual and peak electricity demand of both a hospital building within the Macclesfield Hospital complex and the whole site; investigate the impact of climate change on heating and cooling demand of the hospital buildings and subsequently their impact on annual and peak electricity demand; and examine alternative ways in order to improve hospital energy and thermal performance. Macclesfield Hospital has been selected as a case study, it consists of two main large individual buildings, referred to as the Nucleus and Orthopaedics Buildings. Building energy and thermal models were used in the estimation of energy and internal conditions of an individual hospital building and empirical models for the estimation of hospital site energy demand. The monitoring of internal temperatures revealed overheating for some free-running hospital areas, and failure to comply with the recommended design criteria for heated and air-conditioned rooms. Comparing measured total hospital and total fossil-fuel energy consumption with related benchmarks revealed excess than a typical hospital. The operation of W10 building (an individual building of Macclesfield Hospital) in future climatic conditions, represented by the UKCP09 future weather files, indicated overheating in all hospital wards from 2030 onwards; an annual space heating decrease of 20% by 2030 to 64% by 2080 compared to 2018; and a summer space cooling increase of 12% by 2030 to 70% by 2080 compared to 2018. Likewise, assessing the whole hospitalâs operation in future weather conditions (with no mitigation actions) showed fossil-fuel energy reduction from 6% by 2030 to 15% by 2080 and electricity increase for cooling from 4% by 2030 to 10% by 2080 (ceretis paribus). Further, it was estimated that the current hospital electrical system can cope with future electricity cooling demand, while any possible electrification of the heating system to mitigate climate change will increase the power capability of electrical system up to 100% - depending on heating decarbonisation pathway and heating system selected (the current annual heating demand is more than tripled the annual electricity demand). This study has highlighted some useful operational practices in order to improve thermal and energy performance of a hospital case study including low-energy and low-cost behavioural and operational changes, and low-energy and high-cost building envelope modifications. The decarbonisation process of a complex building may require radical transformation of existing local distribution network, which can be limited by local renewable production on-site or shifting the daily operation of heating in order to deviate heating peak and electricity peak demand.