Science and religion represent important facets of human experience. Yet, they are related in complex and sometimes conflicting ways. The present study examines how religious people think about the science-religion relations by focusing on their epistemic cognition, i.e. thoughts about the nature and justification of knowledge when making sense of competing claims to truth. The study’s main question was whether people express different beliefs with regards to “religiously-neutral” vs. “religiously-loaded” issues in the social-psychological and biological domains. The religiously-neutral issues explored were (a) motivation and work performance, and (b) sugar as the cause of obesity; while the religiously-loaded issues were (c) homosexuality as a disorder, and (d) human evolution. On each of the four issues, undergraduate students from Islamic and Christian backgrounds (N = 317; mean age = 21.4 years; 74.1% female) were asked to express their epistemic beliefs along the three dimensions: (1) ontology, i.e. whether there is a single, objective truth (ontology); (2) fallibility, i.e. whether knowledge of the issue could be wrong; and (3) decidability, i.e. whether there are rational ways to decide on truth. The findings show when thinking about religiously-loaded scientific issues such as homosexuality and evolution, people tend to believe that there is a single objective truth, that their own beliefs are infallible, and that there is no rational method to evaluate knowledge claims. This thinking pattern may be one reason underpinning the difficulty of learning about science concepts which are seen to contradict religious doctrine. Some implications for science education are also entered into the discussion.