© 2014 International Society for Sexual Medicine. Introduction: Little is known about sexual activity and function in women with multiple chronic health conditions. Aim: To examine the impact of multimorbidity on sexual activity and function in middle-aged and older women. Methods: Multiethnic cross-sectional cohort of 1,997 community-dwelling women (mean age of 60.2 [±9.5] years) in California. Structured questionnaires assessed prior diagnoses of common cardiometabolic, colorectal, neuropsychiatric, respiratory, musculoskeletal, and genitourinary conditions. Main Outcome Measures: Sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (i.e., difficulty with arousal, lubrication, orgasm, and pain) were assessed by structured questionnaires. Results: Seventy-one percent of women had two or more diagnosed chronic conditions. Fifty-nine percent reported low sexual desire, 53% reported less than monthly sexual activity, and 47% reported low overall sexual satisfaction. Multimorbidity was associated with increased odds of reporting low sexual desire (OR=1.11, 95% CI=1.06-1.17, per each additional chronic condition), less than monthly sexual activity (OR=1.11, 95% CI=1.05-1.17 per each additional condition), and low sexual satisfaction (OR=1.10, 95% CI=1.04-1.16 per each additional condition), adjusting for age, race/ethnicity, and partner status. Depression and urinary incontinence were each independently associated with low desire (OR=1.53, 95% CI=1.19-1.97, and OR=1.23, 95% CI=1.00-1.52, respectively), less than monthly sexual activity (OR=1.39, 95% CI=1.06-1.83, and OR=1.29, 95% CI=1.02-1.62, respectively), and low sexual satisfaction (OR=1.49, 95% CI=1.14-1.93, and OR=1.38, 95% CI=1.11-1.73, respectively), adjusting for other types of conditions. After adjustment for total number of chronic conditions, age remained a significant predictor of low desire and less than monthly sexual activity, but not sexual satisfaction. Conclusions: Women with multiple chronic health conditions are at increased risk for decreased sexual function. Depression and incontinence may have particularly strong effects on sexual desire, frequency of activity, and satisfaction in women, independent of other comorbid conditions. Women's overall sexual satisfaction may be more strongly influenced by multimorbidity than age.