This study aimed to examine the impact of coronavirus disease 2019 (COVID‐19) on current research participants’ mental health outcomes, ability to adhere to behavioral intervention recommendations, and desire to participate in research. A quantitative/qualitative cross‐sectional survey was used among adults currently enrolled in health‐related research N=250 85% women;  50% currently enrolled in behavioral weight loss intervention). COVID‐19 was perceived as a severe threat by most (62.3%). Related to COVID‐19, 29.6% of participants reported moderate/severe symptoms of anxiety/depression, and 68.4% reported moderate/severe posttraumatic stress disorder (PTSD) symptomatology, with women more likely to demonstrate moderate/severe anxiety/depression P = 0.047) and PTSD symptomatology P = 0.028) relative to men. Those with moderate/severe levels of anxiety/depression P = 0.0154) and distress P = 0.0330) were more likely to report a decreased desire to participate in research. Among those in behavioral interventions, individuals perceiving COVID‐19 as a moderate/severe threat or experiencing moderate/severe depression or PTSD symptomatology were 4 to 19 times more likely to report that COVID‐19 affected their ability to adhere to behavioral recommendations. Qualitative analysis identified four themes describing COVID‐19’s impact on research experiences: transition, remote intervention delivery, ability to adhere to program goals, and research participation interest. These data suggest that participants engaged in health‐related research perceive COVID‐19 as a significant threat, affecting mental health, desire to participate in research, and ability to adhere to intervention recommendations.