In the fall of 2018, cotton fields in Mississippi (MS) exhibiting a range of virus-like symptoms were scouted and cotton plant material tested in the laboratory for possible virus infections. Symptomatic plants exhibited crinkled leaves, shortened internodes, reduced boll set, and abnormal plant growth extending out the top of the cotton canopy. Disease incidence in the fields tested was on the order of < 1% to ? 20%, depending on geographic location. Lab analyses revealed infections by a distinct strain of cotton leafroll dwarf virus (CLRDV), a virus previously reported to affect cotton production in South America and Asia, and most recently reported from Alabama, Georgia and MS. The virus was detected in a pool of 60 samples collected in 13 out of 17 surveyed counties, with an overall incidence exceeding 60%. Analyses of partial sequencing of the viral coat protein and RNA-dependent RNA polymerase genes of several MS isolates suggest high level of conservation. In addition to the initial observation of the virus in infected cotton material during the fall of 2018, winter weeds were screened during the winter of 2019 for CLRDV infections in order to better understand the ecology and epidemiology of this virus. Results of our study, along with data on the same virus from the southern United States, call for an urgent and coordinated multi-state effort to evaluate potential impact of this virus on the U.S. cotton industry.