Women experience greater state negative affect (NA) and physical symptoms during the premenstrual and menstrual phases of the menstrual cycle. Although women use more cannabis during the premenstrual and menstrual phases, no known studies have tested whether this is due to the synergistic effects of heightened NA and using cannabis to cope with increased NA or physical symptoms. This study tested whether state NA interacts with cannabis motives to predict more frequent cannabis use during these phases. Normally cycling women who endorsed past-month cannabis use (N = 40) retrospectively reported NA, cannabis use, and motives for 65 days. Cannabis use was more frequent during the premenstrual (but not menstrual) phase, and cannabis use to manage physical pain/discomfort (physical motives) was greater in the menstrual (but not premenstrual) phase. There were significant interactions between phase, state NA (depression and anger, in separate models), and coping and physical motives. Among women with higher state depression, coping motives were associated with more frequent cannabis use in the ovulatory phase whereas among women with lower state depression, coping motives were associated with more frequent cannabis use in the premenstrual phase. Among women with lower (but not higher) state anger, coping motives were associated with greater cannabis use frequency in the premenstrual phase. Among women with higher state NA, physical motives were associated with more frequent cannabis use in the menstrual (but not premenstrual) phase. Findings support that state NA interacts with motives during high-risk phases and is differentially related to more frequent cannabis use, which has important clinical implications.