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Physics and biology have been the origin of theories that caused tension with religion. As a result, it is important to investigate how spirituality and religiousness affects students’ interest and career path in physics and biology. Using nationally representable data from the Higher Education Research Institute (HERI) 2008 data, we found that spiritual/religious students are significantly less likely to pursue physics as their major while the effect of spirituality/religiousness is positive for choosing biology as a major by first year US students. Data shows that the different effect of spirituality/religiousness on physics and biology majors is related to different career paths for physics and biology majors.