Sick building syndrome is a term that has been described as a complex of non-specific symptoms caused by working in buildings with an adverse indoor environment. This study sought to determine the prevalence and factors associated with sick building syndrome among office workers in Federal House, Kota Kinabalu. A cross-sectional study was conducted from March to July 2010 among 361 office workers in Federal House, Kota Kinabalu. All workers who fulfilled the inclusion and exclusion criteria were included in the study. Respondents were interviewed using questionnaire which was translated to Bahasa Malaysia and validated to identity the socio-demography, work environment and symptoms of sick building syndrome. Indoor air assessment was done to determine the selected chemical and physical parameters. Data were entered and analysed by SPSS 12.0 using descriptive, univariate and multiple logistic regression analyses. The majority of the respondents were female (61.2%) and the staff involved were professional and management group (3.0%), support group I (82.3%) and support group II (14.7%). The mean age was 35.6 (9.22) years and median duration of working at the current workplace was 36 (76.0) months. The prevalence of sick building syndrome was 47.4% (95% CI: 42.2%, 52.5%). Logistic regression analysis showed that significant risk factors associated with sick building syndrome were female (OR: 2.12; 95% CI: 1.34, 3.35; p=0.001), history of allergic (OR: 2.51; 95% CI: 1.30, 4.19; p=0.001) and draught condition in work environment (OR: 2.71; 95% CI: 1.70, 4.32; p=0.001). Physical parameters were above the standard level but concentration of the chemical parameters was within the normal value. The prevalence of sick building syndrome was considered high. Those who had history of allergic, female and exposed to draught condition in work environment were at higher risk of sick building syndrome. Medical follow up should be carried out for the affected worker with regular indoor air monitoring in the workplace.