The purpose of the present study was to examine the rotation strategy in high-level soccer teams during a sequence of three games per week (1st domestic, 2nd European and 3rd domestic). Data were collected during the 2014-15, 2015-16, 2016-17 and 2017-18 competitive season for the soccer teams that were qualified in the quarter finals of the Champions League. Regression analysis showed that when a large number of players participated in the initial list for the three games, more points in the domestic league were lost. Similarly, increasing the changes of players in the initial list between the 1st and the 3rd game and between the 2nd and the 3rd game a negative effect on the domestic league was observed. In contrast, a positive effect of the number of changes of players in the starting line between the 1st and the 2nd game, regarding the total points won, was found. As the average time of the substitutes participated in the game increases in all three games, the total points of the teams are reduced. The biggest time of changes in the 2nd game had a negative impact on the points of European games. In order to achieve a more efficient rotation, coaches should have a qualitative and competitive roster of players. Furthermore, coaches should try to apply different tactics in previous matches in order, as many players as possible, to maintain high levels of homogeneity and competing readiness.