BackgroundDiaphragmatic dysfunction is well documented in patients receiving mechanical ventilation. Inspiratory muscle training (IMT) has been used to facilitate weaning by strengthening the inspiratory muscles, yet the optimal approach remains uncertain. Whilst some data on the metabolic response to whole body exercise in critical care exist, the metabolic response to IMT in critical care is yet to be investigated. This study aimed to quantify the metabolic response to IMT in critical care and its relationship to physiological variables.MethodsWe conducted a prospective observational study on mechanically ventilated patients ventilated for ≥ 72 h and able to participate in IMT in a medical, surgical, and cardiothoracic intensive care unit. 76 measurements were taken on 26 patients performing IMT using an inspiratory threshold loading device at 4 cmH2O, and at 30, 50 and 80% of their negative inspiratory force (NIF). Oxygen consumption (VO2) was measured continuously using indirect calorimetry.ResultsFirst session mean (SD) VO2was 276 (86) ml/min at baseline, significantly increasing to 321 (93) ml/min, 333 (92) ml/min, 351(101) ml/min and 388 (98) ml/min after IMT at 4 cmH2O and 30, 50 and 80% NIF, respectively (p= 0.003). Post hoc comparisons revealed significant differences in VO2between baseline and 50% NIF and baseline and 80% NIF (p= 0.048 andp= 0.001, respectively). VO2increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Every increase in P/F ratio of 1 decreased the intercept VO2by 0.41 ml/min (CI − 0.58 to − 0.24p< 0.001). NIF had a significant effect on the intercept and slope, with every 1 cmH2O increase in NIF increasing intercept VO2by 3.28 ml/min (CI 1.98–4.59p< 0.001) and decreasing the dose–response slope by 0.15 ml/min/cmH2O (CI − 0.24 to − 0.05p= 0.002).ConclusionsIMT causes a significant load-dependent increase in VO2. P/F ratio and NIF impact baseline VO2. The dose–response relationship of the applied respiratory load during IMT is modulated by respiratory strength. These data may offer a novel approach to prescription of IMT.Take home messageThe optimal approach to IMT in ICU is uncertain; we measured VO2at different applied respiratory loads to assess whether VO2increased proportionally with load and found VO2increased by 9.3 ml/min for every 1 cmH2O increase in inspiratory load from IMT. Baseline NIF has a significant effect on the intercept and slope, participants with a higher baseline NIF have a higher resting VO2but a less pronounced increase in VO2as the inspiratory load increases; this may offer a novel approach to IMT prescription.Trial registration ClinicalTrials.gov, registration number: NCT05101850. Registered on 28 September 2021,https://clinicaltrials.gov/ct2/show/NCT05101850Supplementary InformationThe online version contains supplementary material available at 10.1186/s40635-023-00522-6.