Background <p>Estimating secondary attack rates is essential for assessing the spread potential of mpox during an outbreak. The objective of the study was to assess secondary attack rates after mpox exposure in multiple settings worldwide.</p> Methods <p>A systematic review was conducted for studies published between May 2022 and September 2024 and reporting mpox exposure data. The levels and types of exposure were defined as per the study description.</p> Results <p>A total of 62 studies including 8712 mpox exposures were included. Out of 8712 exposures, 239 were associated with mpox infection (secondary attack rate of 2.74%). The rates were highest in household setting (4.02%), intermediate in congregate/community setting (2.50%), and lowest in healthcare setting (0.81%). The rates were highest in the African region (8.00%), intermediate in the European region (4.23%), and lowest in the American region (1.10%). Clade data were available in 17 (27.42%) studies; mainly clade IIb (15 studies) and to less extent clades Ia and Ib (one study each). Secondary attack rates were higher among individuals reporting sexual contact (11.35%) compared with non-sexual contact (1.34%, <i>p</i> &lt; 0.001). Non-sexual contact exposures (83.17%) were more frequent (<i>p</i> &lt; 0.001) than sexual contact exposures (13.66%, <i>p</i> &lt; 0.001).</p> Conclusions <p>The overall mpox secondary attack rate in the published data from the 2022–2024 multi-country outbreak is relatively low (&lt; 3%). While exposures involving non-sexual contact were more prevalent in all settings, sexual contact was responsible for the majority of secondary infections in household and congregate/community settings. The findings may guide mpox preventive and control activities in different settings.</p> Clinical trial <p>Not applicable.</p>