The purpose of the present study is two-fold. First, we evaluated whether 8-weeks of combined training (high-intensity intermittent plus strength training) may change brain derived neurotropic factor (BDNF) and lipid parameters (triacylglycerol, HDL-c and non-HDL) in a fasted state. Second, we investigated the effect of an acute session of high-intensity intermittent exercise followed by strength training on systemic BDNF and lipid parameters pre- and post 8-weeks of training. Twenty-one healthy and physically active men were divided into two groups: high-intensity intermittent exercise combined with strength training (HSG; n = 11) and control (CG; n = 10). The HSG exercised for one minute at 100% of speedVO₂max (sVO₂max) interspersed with one minute of passive recovery followed by strength training (8 exercises with 8-12 repetition maximum loads) for 8-weeks. Heart rate variability, blood pressure, lipid profile, and BDNF concentrations were measured in the fasted state pre- and post-exercise and before and after the 8-week training period. After 8-weeks of exercise training, there was an increase in spectral high frequency component (ms²) and RR interval (p < 0.05), a decreased spectral low frequency component (nu) and heart rate values (p < 0.05), an increase in HDL-c (p < 0.001), and lower BDNF concentrations (p < 0.001). These results suggest that 8-weeks of high-intensity intermittent exercise combined with strength exercise is an effective protective cardio-metabolic strategy capable of increasing HDL-c and BDNF concentrations after an acute exercise session. In the long-term, the modulation on BDNF and HDL-c concentrations may be a determining factor for protection against neurological and cardiovascular diseases.

• The combination of these two modalities in the same exercise session is often used by athletes, recreationally active individuals, and coaches.

• Present knowledge about the combination of aerobic and strength exercise and the influence of intensity on the physiological parameters is insufficient, especially in relation to the practice of high intensity exercise and the higher organic stress imposed.

• The results of this investigation will allow health professionals to use this protocol in an objective and safe way for the purpose of exercise prescription.