Background: CIPN is a dose-limiting toxicity with no established treatments and limited knowledge of risk factors. Exercise during chemotherapy may mitigate CIPN, but it is unknown whether pre-treatment physical activity protects against CIPN. This secondary analysis examines whether physical activity before paclitaxel predicts short- and long-term CIPN symptom severity. Methods: 200 women with non-metastatic breast cancer (52±10 years) receiving paclitaxel with curative intent rated their CIPN (0-10 severity of numbness/tingling in the past week) three times—within 1 week pre-paclitaxel, and within 1 month and 6 months post-paclitaxel. We used linear regression to test whether pre-paclitaxel patient-reported physical activity (Aerobic Center Longitudinal Study) predicted CIPN symptoms (either within 1 month or 6-months post-paclitaxel) controlling for pre-paclitaxel neuropathy, age, BMI, diabetes (yes/no), and cumulative paclitaxel dose. Results: CIPN symptom severity increased significantly from pre- to post-paclitaxel (+3.6 units; p< 0.001) and from pre- to 6-month follow-up (+2.08; p< 0.0001). This is a high level of development of CIPN considering that a 0.5-unit change is clinically significant. Each additional 15 min/day of physical activity pre-paclitaxel was associated significantly less severe CIPN symptoms at post-paclitaxel (-0.5; p= 0.0002) and 6 months follow-up (-0.25; p= 0.09). Each additional 10 years of age was associated with significantly more severe CIPN symptoms at post-paclitaxel (+0.8, p< 0.0001) and 6-month follow-up (+0.9; p< 0.0001) controlling for pre-paclitaxel neuropathy, physical activity, BMI, diabetes, and paclitaxel dose. Conclusions: Breast cancer patients who are more physically active pre-paclitaxel experience less severe CIPN immediately and 6 months post-paclitaxel. Physical activity may be especially important for older patients because CIPN severity increases with age. Clinicians prescribing paclitaxel should ask patients about pre-treatment physical activity levels because it may lead to greater treatment tolerability.