Background: Obsessive-compulsive disorder (OCD) is a widespread mental illness that affects millions of people worldwide. It's onset and peak are during the late teens, making university students a priority target. Nursing students are at greater risk for developing OCD while COVID-19 is expected to more exaggerate symptoms, mainly with extra hygiene and cleanliness practices. Aim: Evaluate the effect of mindfulness skills on self-efficacy and suicidal ideation among first-year nursing students with obsessive-compulsive symptoms during the COVID-19 pandemic. Methods: A quasi-experimental design (one group pre/post-test was used to achieve the aim of the study. The study was conducted at Faculty of Nursing at Menoufia University, which is affiliated to the Ministry of Higher Education in Egypt. A purposive sample of 78 nursing students with obsessive-compulsive symptoms was included. Four tools were used: 1) The Arabic Obsessive-Compulsive Scale, 2) Suicidal Ideation Scale, 3) Self-Efficacy scale, 4)Mindfulness scale, in addition to demographic characteristics. Results: Post-implementation of mindfulness skills, there was a highly statistically significant improvement in self-efficacy and mindfulness skills among studied students (P < 0.001). While there was a highly statistically significant reduction in obsessive-compulsive symptoms and suicidal ideation post-implementation of the mindfulness skills compared to pre-implementation (P = 0.000). Conclusion: The mindfulness skills had a positive effect on improving self-efficacy and decreasing suicidal ideation and obsessive-compulsive symptoms among first-year nursing students during the COVID-19 pandemic. Further studies were needed at all nursing faculties for early identification of students with obsessive-compulsive symptoms and to assist them to overcome their difficulties using mindfulness skills.