Abstract Background Respiratory rate is among the first vital signs to change in deteriorating patients. The aims of this study were to evaluate the accuracy of respiratory rate measurements using a specifically dedicated reflection-mode photoplethysmographic signal analysis in a pathological condition (PPG-RR) and to validate its implementation within medical devices. Methods This study is derived from a data mining project, including all consecutive patients admitted to our ICU (ReaSTOC study, ClinicalTrials.gov identifier: NCT02893462). During the evaluation phase of the algorithm, PPG-RR calculations were retrospectively performed on PPG waveforms extracted from the data warehouse and compared with RR reference values. During the prospective phase, PPG-RR calculations were automatically and continuously performed using a dedicated device (FreeO2, Oxynov, Québec, QC, Canada). In all phases, reference RR was measured continuously using electrical thoracic impedance and chronometric evaluation (Manual-RR) over a 30-s period. Results In total, 201 ICU patients’ recordings (SAPS II 51.7 ± 34.6) were analysed during the retrospective evaluation phase, most of them being admitted for a respiratory failure and requiring invasive mechanical ventilation. PPG-RR determination was available in 95.5% cases, similar to reference (22 ± 4 vs. 22 ± 5 c/min, respectively; p = 1), and well correlated with reference values (R = 0.952; p < 0.0001), with a low bias (0.1 b/min) and deviation (± 3.5 b/min). Prospective estimation of the PPG-RR on 30 ICU patients’ recordings was well correlated with the reference method (Manual-RR; r = 0.78; p < 0.001). Comparison of the methods depicted a low bias (0.5 b/min) and acceptable deviation (< ± 5.5 b/min). Conclusion According to our results, PPG-RR is an interesting approach for ventilation monitoring, as this technique would make simultaneous monitoring of respiratory rate and arterial oxygen saturation possible, thus minimizing the number of sensors attached to the patient. Trial registry number ClinicalTrials.gov identifier NCT02893462