Pressure ulcer (PU) prevention in the intensive care unit (ICU) is an important clinical issue as critically unwell patients are at high risk of developing PUs. However, current methods of PU detection are limited, especially for early detection. This study aimed to establish the correlation between Interleukin-1α (IL-1α)/total protein (TP) and sub-epidermal moisture (SEM) measurements in the early identification of PUs in ICU patients. This study employed an observational research design using the STROBE guidelines. Following ethical approval, 53 participants were recruited and sebum was obtained using Sebutape from weight-bearing areas (sacrum, heels and a control site). SEM measurements were taken from the same anatomical sites. Both measures were taken at the same time and participants were followed up for 5 days, or until discharge or death. Correlations between SEM delta measurements, IL-1α, TP and PU incidence and other demographic information were explored using Spearman's correlation for data not normally distributed, and Pearson's R correlation coefficient for normally distributed data. Mean baseline SEM delta measurements indicate abnormal readings for all anatomical sites except the control site, consistent with previous studies. Mean baseline IL-1α/TP readings were higher for the sacrum versus both heels and, on average, readings were higher for the control site versus all other anatomical locations. This is conflicting, given that the control site was non-weight bearing. There were very weak or weak correlations between SEM delta measurements and IL-1α/TP readings. SEM measurements are quick and easy to obtain and results are instant, however Sebutape sampling takes significantly longer and is challenging to conduct among haemodynamically unstable patients. Obtaining SEM measurements is more practical and feasible than Sebutape sampling to assess for the presence of inflammation.