Background: Androgen deprivation therapy (ADT) is commonly used for the management of prostate cancer (PCa). Despite its benefits, ADT can lead to a range of side effects that have prominent determents on patient quality of life, specifically fatigue. Fatigue is a multidimensional symptom that influences a patient’s psychological and physical well-being, including the inability to perform daily activities due to lack of energy. This analysis evaluates associations between patient-reported fatigue and remotely monitored objective activity in PCa patients. Methods: This is a secondary analysis ofa multi-site observational cohort study (DigiPRO) among men diagnosed with advanced PCa, initiating ADT within 6 months, conducted between 12/2020 and 4/2023. Eligible patients wore an activity monitor (Fitbit Charge HR 4) continuously for the 12-week study and completed NIH PROMIS fatigue surveys via REDCap, which included Likert-scale questions (8 items, range 1-5 (worse)) about fatigue severity and interference, at baseline, 4, 8, and 12 weeks. PROMIS scores were converted to standardized T-scores (mean 50: SD: 10). Pearson correlation coefficients were calculated, and multivariable logistic regression models were fit to evaluate associations between activity and fatigue T-scores. Results: 40 patients were included in the analysis (median age: 70 yrs, range 51-85; 37% Black or African American/63% White, 10% Hispanic/90% non-Hispanic White). 11 patients reported high levels of fatigue (T-Score>60) at least once over the course of the study and 20% of patients experienced an increase > 5 T-score points from baseline, indicating clinically meaningful deterioration. Higher fatigue T-scores were negatively correlated with higher daily step counts (r=-0.6, p=0.003) and calories expended (r=-0.5, p=0.002) and positively correlated with increased sedentary time (r=0.5, p=0.002) at baseline. Lower baseline step counts were significantly associated with any occurrence of worsening patient fatigue over the study period (OR: 2.08, 95% CI 1.12-3.8, per 1000 step decrease, p=0.02) after adjusting for age and race. Patients who reported worsening fatigue had a mean step count of 3,426 compared to 5,664 steps/day among those who reported stable or improving fatigue (p=0.02). Conclusions: Findings from this analysis suggest that objective measures of daily activityare correlated with patient-reported fatigue and predict worsening fatigue over time. Routine collection and monitoring of patient-reported fatigue and daily activity during ADT may help identify patients at increased risk for worsening fatigue. More research is needed to determine the role of wearable activity monitors as potential interventions and for real time monitoring to help manage fatigue and other symptoms during ADT. Clinical trial information: NCT04575402.