Renal failure patients provide a good model of fluid overload with the process of hemodialysis leading to central hypovolemia. This study aims to assess if hemodialysis induces identifiable changes in ear photoplethysmographic waveform variability (PPGV). The results are based on data collected from 10 kidney failure patients undergoing regular hemodialysis; classified as either fluid removal or non-fluid removal patients. Six minutes of continuous photoplethysmography (PPG) signals were recorded at pre-dialysis, end of dialysis and at regular intervals of 20 minutes during hemodialysis. Baseline and amplitude variabilities were derived from the PPG waveform. Frequency spectrum analysis was applied to these variability signals and spectral powers were then calculated from low frequency (LF), mid frequency (MF) and high frequency (HF) bands. The results indicate that in fluid removal patients, LF (p = 0.04), MF (p = 0.03) and HF (p = 0.0003) powers of amplitude ear PPGV (expressed in mean-scaled units) showed a significant increase at the end of dialysis compared to pre-dialysis. No significant change was observed in non-fluid removal patients. A moderate correlation was found between relative blood volume (RBV) and HF power (median R = 0.64, p 〈 0.05). This study suggests that ear PPG may be a suitable monitor of the systemic circulation and can provide a non-invasive tool to detect blood volume loss.