Abstract Interleukin 6 (IL-6) is a type of interleukin that functions as both a pro-inflammatory and anti-inflammatory cytokine. It is encoded by the IL6 gene in humans. Both COVID-19 infection and S-Protein Based Vaccines for COVID-19 were found to induce the production of pro-inflammatory IL-6, and also, strenuous exercise was found to induce IL-6 secretion by the skeletal muscles via lactate. Exercise causes skeletal muscle cells to release IL-6, and it raises the plasma concentration of IL-6 100 times higher than at rest. Exercise-induced IL-6 release is highly correlated with exercise intensity and duration; thus, IL-6 is regarded as an energy sensor released by contracting muscles. Although, COVID-19 infection and S-Protein Based Vaccines for COVID-19 have similar pathological effects, such as myocardial infarction, thrombotic and coagulation abnormalities (deep thrombosis), but these adverse effects are rarely associated with S-Protein Based Vaccines for COVID-19. Recently, it was shown that most patients who experienced myocarditis after the COVID-19 vaccine were young male youth aged 16 to 29 years had the highest incidence of myocarditis. Interestingly, It was observed that IL-6 was linked to adverse effects such as thrombosis and myocarditis, both of which are similar to that was caused by COVID-19 infection, and that S-Protein based vaccines for COVID-19. Here, we propose a testable hypothesis that strenuous exercise could be a risk and cofactor helping in the existence of these adverse effects in young people such as myocarditis and thrombosis via induction of the secretion of proinflammatory IL-6. In our retrospective and prospective observational study, we will assess the possible correlation among strenuous exercise, IL-6, myocarditis, and thrombosis. The study will be multi-center and will involve a young patient who will be vaccinated with first, second, and third doses of S-Protein Based Vaccines for COVID-19 (Moderna and Pfizer-BioNTech vaccine). Pfizer and BioNTech have successfully developed the BNT162b2 mRNA vaccine, which consists of the full-length S glycoprotein with the K986P and V987P mutation sites. Also, Moderna's mRNA-1273 vaccine contains the coding sequence for an S glycoprotein stabilized by a pair of proline substitutions (K986P/V987P), a transmembrane anchor, and an intact S1-S2 cleavage site .