Post-COVID-19 syndrome (long COVID) describes ongoing symptoms for 12 or more weeks following infection with SARS-CoV-2. Respiratory-related symptoms including breathlessness [1], exercise intolerance and ventilatory dysfunction [2] are common in long COVID. Further, cells at the primary site of oxygen sensing (carotid bodies) are susceptible to SARS-CoV-2 infection [3]. We aimed to determine whether long COVID patients have altered carotid chemoreceptor sensitivity, by assessing resting hypoxic ventilatory response and ventilatory efficiency during exercise. Fourteen long COVID patients (3 male, 42 ± 12 years) and eight control participants (did not develop long COVID post-infection) gave written informed consent to participate in an ethically approved study (NHS REC). The control group was supplemented by six healthy individuals who undertook the same experimental procedures in the same laboratory, prior to the pandemic (in total; 2 male, 35 ± 13 years, P=0.1195 for age versus patient group). Participants did not have pre-existing respiratory or cardiovascular disease and resting lung function (spirometry) was similar between the groups. Transient hypoxia was achieved by supplementing inspired air with 100% N₂ for 5-8 short periods, lasting 5-30 seconds, reducing S_PO₂ to nadirs of between 65 and 99%. Breath-by-breath minute ventilation (V_E), tidal volume and breathing frequency, and beat-to-beat heart rate and blood pressure, were monitored during N₂ supplementation and for one minute afterwards. The 95^th percentile of these variables and the nadir S_PO₂ were determined for each hypoxic period and entered into a simple linear regression, where the slope defined response to hypoxia (peripheral chemoreceptor sensitivity). The V_E response to hypoxia was greater in long COVID patients versus controls (-0.44 ± 0.23 versus -0.17 ± 0.13 L/min/S_PO₂, Figure; P=0.0007, independent samples T-test), demonstrating greater ventilation for a given fall in S_PO₂. This difference was caused by a larger tidal volume response, as breathing frequency response was similar. Heart rate and blood pressure responses were also unchanged (Figure). Participants performed a maximal exercise test (upright cycle ergometer, ramp protocol to volitional exhaustion). Long COVID patients had a lower peak VO₂ versus controls (18.6 ± 4.7 versus 26.7 ± 7.4 ml/kg/min, P=0.0015), despite reaching a similar peak V_E (66.4 ± 22.4 versus 71.5 ± 29.2 L/min, P=0.6012), respiratory exchange ratio (1.27 ± 0.09 versus 1.28 ± 0.11, P=0.7483), and percentage of predicted heart rate (92 ± 9 versus 97 ± 6 %, P=0.1326) to the control group. V_E/VCO₂ slope (ventilation for a given expired CO₂ volume) was greater in the long COVID group versus controls (37.8 ± 4.4 versus 31.4 ± 4.8, P=0.0008), indicating reduced ventilatory efficiency in the long COVID group. Furthermore, V_E/VCO₂ slope was correlated with hypoxic ventilatory response, such that enhanced chemoreflex sensitivity was associated with poorer ventilatory efficiency during exercise (r=0.54, P=0.0037, Pearson’s correlation, n=28). These data demonstrate that long COVID is associated with high peripheral chemoreflex sensitivity and reduced ventilatory efficiency during exercise. These changes could underlie the respiratory symptoms of long COVID such as dyspnoea and exercise intolerance. Targeting the carotid body to reduce its sensitivity may provide benefit to long COVID patients.