High-containment laboratories (HCLs) conduct critical research on infectious diseases, provide diagnostic services, and produce vaccines for the world’s most dangerous pathogens, often called high-consequence pathogens (HCPs). The modernization of HCLs has led to an increasingly cyber-connected laboratory infrastructure. The unique cyberphysical elements of these laboratories and the critical data they generate pose cybersecurity concerns specific to these laboratories. Cyberbiosecurity, the discipline devoted to the study of cybersecurity risks in conjunction with biological risks, is a relatively new field for which few approaches have been developed to identify, assess, and mitigate cyber risks in biological research and diagnostic environments. This study provides a novel approach for cybersecurity risk assessment and identification of risk mitigation measures by applying an asset-impact analysis to the unique environment of HCLs. First, we identified the common cyber and cyberphysical systems in HCLs, summarizing the typical cyber-workflow. We then analyzed the potential adverse outcomes arising from a compromise of these cyber and cyberphysical systems, broadly categorizing potential consequences as relevant to scientific advancement, public health, worker safety, security, and the financial well-being of these laboratories. Finally, we discussed potential risk mitigation strategies, leaning heavily on the cybersecurity materials produced by the Center for Internet Security (CIS), including the CIS Controls®, that can serve as a guide for HCL operators to begin the process of implementing risk mitigation measures to reduce their cyberbiorisk and considering the integration of cyber risk management into existing biorisk management practices. This paper provides a discussion to raise awareness among laboratory decision-makers of these critical risks to safety and security within HCLs. Furthermore, this paper can serve as a guide for evaluating cyberbiorisks specific to a laboratory by identifying cyber-connected assets and the impacts associated with a compromise of those assets.