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Aim Alpha-thalassaemia is known to reduce intra-erythrocyte Hb S (sickle haemoglobin) concentration in sickle cell trait ( SCT) subjects. Because Hb S was shown to increase oxidative stress, the purpose of this study was to assess the effects of the coexistence of α-thalassaemia and SCT on oxidative stress markers and nitric oxide ( NO) metabolism after an acute physical exercise. Methods Forty subjects (age: 23.5 ± 2.21 years), SCT carriers ( Hb AS) or healthy subjects ( Hb AA), with (-α T) or without (- Nα T) an associated α-thalassaemia took part in the study. Plasma markers of oxidative stress [advanced oxidation protein products ( AOPP), protein carbonyl, malondialdehyde ( MDA) and nitrotyrosine], anti-oxidant defences and NO metabolism ( NOx) were measured at rest ( Trest), immediately following an incremental maximal exercise test ( Tex) and during recovery ( T1h, T2h and T24h). Results Malondialdehyde expressed as the percentage of changes from baseline was significantly higher in the Hb AS- Nα T compared with Hb AS-α T during recovery (+36.3 ± 14.1% vs. −1.8 ± 13.2% at T1h, P = 0.02; +36.6 ± 13.4% vs. −11.4 ± 12.5% at T2h, P = 0.004 and +24.1 ± 12.3% vs. −14.4 ± 11.5% at T24h, P = 0.02 in Hb AS- Nα T vs. Hb AS-α T). Compared with Hb AS- Nα T, Hb AS-α T had a higher NOx change from baseline at Tex (−23.4 ± 20.6% vs. +57.7 ± 19.3%, respectively; P = 0.005) and lower nitrotyrosine change from baseline at T1h (+7.2 ± 22.2% vs. +93.5%±29.3%, respectively; P = 0.04). Conclusion All these data suggest that the presence of α-thalassaemia may blunt the higher level of oxidative stress and the impaired bioavailability of NO observed in the SCT carriers. [ABSTRACT FROM AUTHOR]