The purpose of this study was to examine job stress and mental health among high-skilled foreign workers (HFWs) in Japanese workplace. Questionnaire including items about job stressors (9 factors), social supports (supervisor, co-worker, family/friends) and satisfaction (work, family) and stress reactions (anxiety, depression, psychosomatic symptoms) was administered to 274 workers mainly living in Tokyo (126 HFWs and 150 Japanese workers). ‘Quantitative overload’ and ‘workplace environment’ caused significantly lower levels of job stress, while ‘qualitative overload’ and ‘interpersonal relationships’ produced significantly higher levels of job stress among HFWs than Japanese workers. Interestingly, not only 2 job stress factors (‘job fitness’, ‘rewarding job’) and ‘job satisfaction’ but also 2 stress reactions (‘depression’ and ‘psychosomatic symptoms’) were higher among HFWs than Japanese workers. ‘Interpersonal relationships’ which is the major stressor among Japanese workers was not correlated with either of the stress reaction factors, while ‘qualitative overload’ was correlated with ‘anxiety’ only. This study suggests possibility that HFWs’ job stress is associated with difference of cognitive appraisal between HFWs and Japanese workers or of cross-cultural contexts embedded in workplace.