The COVID-19 pandemic and measures aimed at its mitigation, such as physical distancing, have been discussed as risk factors for loneliness, which increases the risk of premature mortality and mental and physical health conditions. To ascertain whether loneliness has increased since the start of the pandemic, this study aimed to narratively and statistically synthesize relevant high-quality primary studies. This systematic review with meta-analysis was registered at PROSPERO (ID CRD42021246771). Searched databases were PubMed, PsycINFO, Cochrane Library/Central Register of Controlled Trials/EMBASE/CINAHL, Web of Science, the World Health Organization (WHO) COVID-19 database, supplemented by Google Scholar and citation searching (cutoff date of the systematic search December 5, 2021). Summary data from prospective research including loneliness assessments before and during the pandemic were extracted. Of 6,850 retrieved records, 34 studies (23 longitudinal, 9 pseudolongitudinal, 2 reporting both designs) on 215,026 participants were included. Risk of bias (RoB) was estimated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool. Standardized mean differences (SMD, Hedges' g) for continuous loneliness values and logOR for loneliness prevalence rates were calculated as pooled effect size estimators in random-effects meta-analyses. Pooling studies with longitudinal designs only (overall N = 45,734), loneliness scores (19 studies, SMD = 0.27 95% confidence interval = 0.14-0.40, Z = 4.02, p < .001, I 2 = 98%) and prevalence rates (8 studies, logOR = 0.33 0.04-0.62, Z = 2.25, p = .02, I 2 = 96%) increased relative to prepandemic times with small effect sizes. Results were robust with respect to studies' overall RoB, pseudolongitudinal designs, timing of prepandemic assessments, and clinical populations. The heterogeneity of effects indicates a need to further investigate risk and protective factors as the pandemic progresses to inform targeted interventions. Public Significance Statement This synthesis of international research with a focus on longitudinal study designs shows small, but robust increases in loneliness during the COVID-19 pandemic across gender and age groups. As loneliness jeopardizes mental and physical health, these findings indicate that public health responses to the continuing pandemic should include monitoring of feelings of social connectedness and further research into risk and protective factors.