OBJECTIVES: To investigate factors associated with reporting lacking interest in sex and how these vary by gender. SETTING: British general population. DESIGN: Complex survey analyses of data collected for a cross-sectional probability sample survey, undertaken 2010-2012, specifically logistic regression to calculate age-adjusted OR (AOR) to identify associated factors. PARTICIPANTS: 4839 men and 6669 women aged 16-74 years who reported ≥1 sexual partner (opposite-sex or same-sex) in the past year for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). MAIN OUTCOME MEASURE: Lacking interest in sex for ≥3 months in the past year. RESULTS: Overall, 15.0% (13.9-16.2) of men and 34.2% (32.8-35.5) of women reported lacking interest in sex. This was associated with age and physical and mental health for both men and women, including self-reported general health and current depression. Lacking interest in sex was more prevalent among men and women reporting sexually transmitted infection diagnoses (ever), non-volitional sex (ever) and holding sexual attitudes related to normative expectations about sex. Some gender similarities in associated relationship and family-related factors were evident, including partner having had sexual difficulties in the last year (men: AOR 1.41 (1.07-1.86); women: AOR 1.60 (1.32-1.94)), not feeling emotionally close to partner during sex (men: 3.74 (1.76-7.93); women: 4.80 (2.99-7.69) and ease of talking about sex (men: 1.53 (1.23-1.90);women: 2.06 (1.77-2.39)). Among women only, lack of interest in sex was higher among those in a relationship of >1 year in duration and those not sharing the same level of interest (4.57 (3.87-5.38)) or preferences (2.91 (2.22-3.83)) with a partner. CONCLUSIONS: Both gender similarities and differences were found in factors associated with lacking interest in sex, with the most marked differences in relation to some relationship variables. Findings highlight the need to assess, and if appropriate, treat lacking interest in sex in a holistic and relationship-specific way.