The COVID-19 pandemic has caused significant changes in global sustainability, but specifically, this study analyses the impact of lockdown on health and behavior in the game of football. The 2020/2021 Italian football competitive season (indicated as “post-COVID”), taking place following an obliged lockdown and longer than the normal summery season break, was characterized by very short recovery times and was compared to the 2018–2019 “pre-COVID” season, which had a regular course. The comparisons were about anthropometric and hormonal responses, muscle damage, and the physical performance of players in the major league (Serie A), and were made considering two extreme points of the competitive seasons: before the preparatory period (T0) and at the end of the season (T1). Turning to the results, it is significant to note the following: (1) body fat percentage was lower at the start (T0) of the post-COVID season than at the start of the pre-COVID season. During both seasons, serum CK and LDH increased in T1 and were significantly higher in both T0 and T1 of the post-COVID season. (2) Cortisol and testosterone concentrations increased in both seasons from T0 to T1; however, in the post-COVID season, concentrations of both were higher than in the previous season. The testosterone to cortisol ratio increased at the end of the pre-COVID season, whilst strongly decreasing at T1 of the post-COVID season. (3) Blood lactate concentrations significantly decreased during the pre-COVID season but remained unchanged during the post-COVID season. We may conclude that the enforced suspension period and the consequent rapid resumption of all activities influenced the physical and physiological state of professional footballers.