Background: Pressure injury risk assessment tools have several well-known limitations. As a result, new methods of assessing risk are emerging, including the use of sub-epidermal moisture measurement to detect localized oedema. Aims: To assess the daily variation in sacral sub-epidermal moisture measurement over five days and establish if age and prophylactic sacral dressing use influenced these measurements. Methods: As part of a larger randomized controlled trial of the use of prophylactic sacral dressings, a longitudinal observational substudy was undertaken in hospitalized medical and surgical adult patients at risk of pressure injury. The substudy was conducted in consecutively recruited patients from 20 May 2021 to 9 November 2022. Using the SEM 200 (Bruin Biometrics LLC), daily sacral sub-epidermal measurements for up to five days were completed. Two measurements were generated, the most recent sub-epidermal moisture measurement and, after at least three measurements, a delta value, the difference between the highest and lowest values. The delta measurement was the outcome, with a delta of ≥ 0.60 considered abnormal, increasing the risk of pressure injury development. A mixed analysis of covariance was undertaken to determine if there was any change in delta measurements over the five days and to determine if age and sacral prophylactic dressing use influenced sub-epidermal moisture delta measurement. Results: A total of 392 participants were included in this study; 160 (40.8%) patients had completed five consecutive days of sacral sub-epidermal moisture delta measurements. In total, 1324 delta measurements were undertaken across the five study days. In total, 325 of 392 patients (82.9%) had experienced one or more abnormal delta. Furthermore, 191 (48.7%) and 96 (24.5%) of patients experienced abnormal deltas for two or more and three or more consecutive days. There was no statistically significant variation in sacral sub-epidermal moisture delta measurements over time; increasing age and prophylactic dressing use did not influence sub-epidermal moisture deltas over the five days. Conclusion: If only one abnormal delta was used as a trigger, about 83% of patients would have received additional pressure injury prevention strategies. But, if a more nuanced approach to responding to abnormal deltas is taken, between 25 and 50% of patients may receive additional pressure injury prevention, representing a more time and resource efficient approach.