The study sought to determine factors that affected academic performance of in-service students in Science Education Degree Programme at the University of Zambia. The study was motivated by the knowledge gap as to why it was common in Science Education at the University of Zambia for both school leavers and in-service students to be excluded from school, repeat courses or change to non-science programmes due to poor academic performance. In order to have in-depth understanding of the phenomenon being studied, a case study design was used. Both qualitative and quantitative research methods were used to collect data from 88 respondents. Simple random and purposive sampling procedures were used to select the study sample. 80 students were selected by simple random sampling procedure. This procedure was used in order to allow all the students to have an equal chance to be selected for the sample. Purposive sampling procedure was used in order to select the lecturers and tutors. The procedure was used to select the lecturers and tutors because they were the only ones with adequate knowledge about Science Education Degree programme at the level of lecturers which the researchers were inquiring. The study findings showed that several factors adversely affected academic performance of the in-service students who were studying Science Education Degree programme at the University of Zambia. These included; inadequate supportive lecturer-student relationship, combining Science with Mathematics in one programme, dilapidated classroom infrastructure especially the laboratories, too much content in the curriculum of which some was considered irrelevant to what was taught in schools, personal life problems and responsibilities, pace at which material were being delivered in class was too fast for them, poor attendance to lectures and laboratories by students themselves. In addition, students were stressed by their own poor academic performance and they had difficult to comprehend advanced concepts in Mathematics. Based on these findings, the study recommended that (1) the school of Education should introduce a programme in Science Education specifically for student training to be teachers of science, (2) review its current curriculum so that its content relates with what is taught in schools, (3) in order to support the students who felt the pace of delivery was too fast for them, there was need to encourage group discussion among them,(4) the school should provide a conducive learning environment by preparing classroom infrastructure and providing adequate learning materials.