Purpose: This investigation examined the longitudinal changes and interrelationships of salivary and self-report monitoring measures across a professional football season. Methods: Measures were collected biweekly from 18 senior professional male players across a 6-wk preseason and eight 5-wk in-season mesocycles and analyzed using a linear mixed-effects model. Results: Analysis identified a small (P = 0.003) cross-season suppression of salivary immunoglobulin A, small reductions to salivary α-amylase (P = 0.047) and salivary cortisol (P = 0.007), and trivial changes to salivary testosterone (P > 0.05). The testosterone/cortisol ratio typically responded inversely to changes in player workload. Self-report measures of fatigue (P = 0.030), sleep quality (P = 0.003), and muscle soreness (P = 0.005) improved (ES = small) across the first half of the season. Fatigue and sleep measures were most consistently related to hormonal measures (R2 = 0.43-0.45). For these relationships, increases in cortisol were associated with compromised self-report responses, whereas increases in testosterone/cortisol were associated with improved responses. Nonlinear relationships were identified for fatigue with immunoglobulin A (P = 0.017; ES = trivial) and testosterone (P = 0.012; ES = trivial), for sleep quality with testosterone (P < 0.001; ES = trivial), for muscle soreness with testosterone (P = 0.012; ES = trivial), and for the self-report inventory sum with testosterone (P = 0.027; ES = trivial). For these relationships, self-report responses were optimal at mean immunoglobulin A and testosterone levels, and very low levels (-2 SD) exerted the most compromising effects. Conclusions: Players can experience a chronic cross-season suppression of mucosal immunity. Salivary immunoglobulin A, testosterone, cortisol, and testosterone/cortisol measures relate to self-report measures of fatigue, sleep quality, and muscle soreness. In-season reductions in testosterone, cortisol, and testosterone/cortisol or increases in cortisol among elite football players could be used to indicate the need for reduced workload, which might lead to improved well-being.