The purpose of this study was to examine the effect of a soccer small-sided game (SSG) on performance, inflammatory, muscle damage and hormonal indicators. Twenty-two male soccer players participated and were assigned to either experimental (EXP = 12) or control (CON = 10) groups. Subjective fatigue (RPE) and lactate (La¯) were measured during the SSG; vertical squat jump (SJ), 20-m sprint, creatine kinase (CK), interleukin-6 (IL-6), cortisol (C), and testosterone (T) were measured before (PRE), after (POST), 24 h, 48 h, and 72 h after the SSG in the EXP group. The heart rate during the SSG reached 92 ± 3% of their HRmax, whereas La¯ and RPE reached 13.02 ± 1.60 mmol·L⁻¹ and 15 ± 1 after SSG, respectively. The IL-6, different among measurements (F (1.04, 11.50) = 504.82, p < 0.001), peaked (3.52 ± 0.43 pg·mL⁻¹ [95%CI; 3.28–3.77]) after the SSG and returned to baseline 24 h later. The CK, different among measurements (F (1.76, 19.32) = 93.96, p < 0.001), peaked (536.58 ± 124.73U·L⁻¹ [95%CI; 466.01–607.15]) 24 h after the SSG and remained significantly higher than PRE condition in POST and up to 72 h later. The T/C ratio, significantly different among measurements (F (1.73, 19.05) = 12.12, p < 0.001), was at its lowest (0.44 ± 0.16 [95%CI; 0.35–0.54]) immediately after the SSG (p < 0.05) and returned to baseline after 24 h. It seems that 48 h (at the most) after an SSG is adequate time for players to recover, and a high training load should be avoided sooner than 24 h after an SSG.