UNLABELLED: This systematic review assessed the psychometric properties and the cross-cultural adaptation of the University of California and Los Angeles Loneliness scale (UCLA-LS) in adults. A systematic search of four electronic databases (PubMed, EMBASE, Scopus, and PsycINFO) was conducted from inception until March 2021. We followed the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines for data extraction and evidence synthesis. Eighty-one studies assessed the validity and reliability of the UCLA-LS, translated into many languages, and applied across several countries/societies. Three versions of the 20-item and nine short versions of the UCLA-LS with 3 to 20 questions were identified. High-quality evidence supported the internal structure of the UCLAs: 4, 6, 7 and 10, while low-to moderate-quality evidence supported the construct validity of the UCLAs: 3, 4, 6, 8, 16 and 20. Moderate-quality evidence supported the test-retest reliability of version 3 UCLA-20 with excellent interclass coefficients values of 0.76-0.93. The UCLAs: 4, 6, 7 and 10 had the most robust internal structure and may therefore be the most useful for informing clinicians and social psychologists engaged in assisting those with loneliness. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-02494-w.