Dyspnoea is frequent and distressing in patients receiving mechanical ventilation, but it is often not properly evaluated by caregivers. Electroencephalographic signatures of dyspnoea have been identified experimentally in healthy subjects. We hypothesized that adjusting ventilator settings to relieve dyspnoea in MV patients would induce EEG changes. This was a first-of-its-kind observational study in a convenience population of 12 dyspnoeic, mechanically ventilated patients for whom a decision to adjust the ventilator settings was taken by the physician in charge (adjustments of pressure support, slope, or trigger). Pre- and post-ventilator adjustment electroencephalogram recordings were processed using covariance matrix statistical classifiers and pre-inspiratory potentials. The pre-ventilator adjustment median dyspnoea visual analogue scale was 3.0 (interquartile range: 2.5-4.0; minimum-maximum: 1-5) and decreased by (median) 3.0 post-ventilator adjustment. Statistical classifiers adequately detected electroencephalographic changes in 8 cases (area under the curve ≥0.7). Previously present pre-inspiratory potentials disappeared in 7 cases post-ventilator adjustment. Dyspnoea improvement was consistent with electroencephalographic changes in 9 cases. Adjusting ventilator settings to relieve dyspnoea produced detectable changes in brain activity. This paves the way for studies aimed at determining whether monitoring respiratory-related electroencephalographic activity can improve outcomes in critically ill patients under mechanical ventilation.