BACKGROUND: Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America-Europe-Australia (NEA) based on studies published during 1981-2013. At that time, there were too few studies with data from South/Central America-Asia-Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE: The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS: We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014-2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973-2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES: Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: -0.87 million/ml/year, 95% CI: -0.89 to -0.86; P < 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (-1.27; -1.78 to -0.77; P < 0.001) and unselected men from SAA (-0.65; -1.29 to -0.01; P = 0.045) and fertile men from NEA (-0.50; -1.00 to -0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (-1.17: -1.66 to -0.68; P < 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (-1.73: -3.23 to -0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (-4.70 million/year; -6.56 to -2.83; P < 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS: This analysis is the first to report a decline in sperm count among unselected men from South/Central America-Asia-Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.