BACKGROUND: Although low temperature and air pollution exposures have been associated with the risk of anxiety, their combined effects remain unclear. OBJECTIVE: To investigate the independent and interactive effects of low temperature and air pollution exposures on anxiety. METHOD: Using a case-crossover study design, the authors collected data from 101,636 outpatient visits due to anxiety in three subtropical Chinese cities during the cold season (November to April in 2013 through 2018), and then built conditional logistic regression models based on individual exposure assessments [temperature, relative humidity, particulate matter (PM(2.5), PM(10)), sulfur dioxide (SO(2)), and nitrogen dioxide (NO(2))] and twelve cold spell definitions. Additive-scale interactions were assessed using the relative excess risk due to interaction (RERI). RESULTS: Both cold spell and air pollution were significantly associated with outpatients for anxiety. The effects of cold spell increased with its intensity, ranging from 8.98% (95% CI: 2.02%, 16.41%) to 15.24% (95% CI: 6.75%, 24.39%) in Huizhou. Additionally, each 10 μg/m(3) increase of PM(2.5), PM(10), NO(2) and SO(2) was associated with a 1.51% (95% CI: 0.61%, 2.43%), 1.58% (95% CI: 0.89%, 2.28%), 13.95% (9.98%, 18.05%) and 11.84% (95% CI: 8.25%, 15.55%) increase in outpatient visits for anxiety. Synergistic interactions (RERI >0) of cold spell with all four air pollutants on anxiety were observed, especially for more intense cold spells. For particulate matters, these interactions were found even under mild cold spell definitions [RERI: 0.11 (95% CI: 0.02, 0.21) for PM(2.5), and 0.24 (95% CI: 0.14, 0.33) for PM(10)]. Stratified analyses yielded a pronounced results in people aged 18-65 years. CONCLUSIONS: These findings indicate that both cold spell and air pollution are important drivers of the occurrence of anxiety, and simultaneous exposure to these two factors might have synergistic effects on anxiety. These findings highlight the importance of controlling air pollution and improving cold-warning systems.