To evaluate how stress related to the coronavirus disease 2019 (COVID-19) pandemic has affected women's menstrual cycles. We hypothesized that women with high levels of COVID-19-related stress would have more menstrual changes compared with those with lower levels of stress. Using a cross-sectional study design, we recruited a representative sample of U.S. adult women of reproductive age (18-45 years) using nonhormonal birth control to participate in an online REDCap (Research Electronic Data Capture, Vanderbilt University) survey. COVID-19-related stress was assessed with the PSS-10-C (COVID-19 Pandemic-related Perceived Stress Scale) and dichotomized as low stress (scores lower than 25) and high stress (scores 25 or higher). Self-reported menstrual outcomes were identified as changes in cycle length, duration, or flow and increased frequency of spotting between cycles. We used χ 2 and Fisher exact tests to compare differences in outcome between the two stress groups and logistic regression models for effect estimates. A total of 354 women of reproductive age across the United States completed both the menstrual and COVID-19-related stress components of our survey. More than half of these women reported at least one change in their menstrual cycles since the start of the pandemic (n=191), and 10.5% reported high COVID-19-related stress (n=37). Compared with those with low COVID-19-related stress, a greater proportion of women with high COVID-19-related stress reported changes in cycle length (shorter or longer; P =.008), changes in period duration (shorter or longer; P <.001), heavier menstrual flow ( P =.035), and increased frequency of spotting between cycles ( P =.006) compared with prepandemic times. After adjusting for age, smoking history, obesity, education, and mental health history, high COVID-19-related stress was associated with increased odds of changes in menstrual cycle length (adjusted odds ratio [aOR] 2.32; 95% CI 1.12-4.85), duration (aOR 2.38; 95% CI 1.14-4.98), and spotting (aOR 2.32; 95% CI 1.03-5.22). Our data also demonstrated a nonsignificant trend of heavier menstrual flow among women with high COVID-19-related stress (aOR 1.61; 95% CI 0.77-3.34). High COVID-19-related stress is associated with significant changes in menstrual cycle length, alterations in period duration, and increased intermenstrual spotting as compared with before the pandemic. Given that menstrual health is frequently an indicator of women's overall well-being, clinicians, researchers, and public health officials must consider the association between COVID-19-related stress and menstrual disturbances.