Lung cancer screening (LCS) with low-dose radiation computed tomography (LDCT) reduces mortality and is recommended for high-risk current and former smokers. Several potential harms associated with LCS have been identified, including the potential for psychological burden. To summarize the current state of the scientific knowledge on psychological burden associated with LCS, we performed a systematic search of the contemporary quantitative and qualitative research literature. We included randomized controlled trials and cohort studies that evaluated the effect of LCS with LDCT on psychological burden and health-related quality of life assessed using validated and nonvalidated measures. PubMed, CINAHL, PsychINFO, and Scopus were searched for English language articles published between 2004 and January 2015. Data abstraction and quality assessment were conducted by 2 independent reviewers. Thirteen studies were included that met our inclusion criteria. Overall, results were variable with some studies reporting worse psychological burden for patients with indeterminate results at prescreening, after screening, and at short-term follow-up (<6 months after screen). These adverse effects diminished or resolved at long-term follow-up (> 6 months after screen). LCS might be associated with short-term adverse psychological burden, particularly after a false positive result. However, these adverse effects diminished over time. The amount of current evidence is small, with limitations in study design and use of outcome measures. More high-quality research is needed to determine the frequency, duration, and overall magnitude of LCS-related psychological burden in nonclinical trial settings.