The aim of this study was to identify the acute physiological responses and activity profiles of football small-sided games (SSG) formats. Ten professional football players participated in 4 variations of SSG (2-, 3-, 4-, and 5-a-side) with an intermittent regime involving 3 × 6-minute bouts with 1 minute of passive planned rest in which the heart rate (HR), rating of perceived exertion (RPE), activity profile, and body load were recorded. The higher percentage of maximum HR values were found in 2- and 3-a-side formats (p ≤ 0.05). The lowest RPE value was found at the 5-a-side, and the highest was found at the 2-a-side (13.48 ± 2.67 and 17.01 ± 1.80, respectively, p ≤ 0.05). The distance covered in the 2-a-side format (598.97 ± 78.91 m) was smaller than in all other formats. The 2-a-side format presented the lowest number of sprints (0.71 ± 0.86) and the 3-a-side the highest (2.50 ± 1.65). Statistically significant differences were found across SSG in the total body load. The 4-a-side presented the highest and the 5-a-side the lowest values (95.18 ± 17.54 and 86.43 ± 14.47, respectively). The body load per minute declined each 2 minutes of play. Maintaining a constant area:player ratio, coaches can use lower number of players (2- and 3-a-side) to increase cardiovascular effects but use higher number of players (4- and 5-a-side) to increase variability and specificity according to the competition demands.