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This MWE works in tex live versions prior to the 2018 version:

\documentclass{article}

\usepackage{fontspec, lipsum}
    \setmainfont{Libertinus Serif}

\begin{document}
\lipsum
\end{document}

In tex live 2018, compiling this results in the error

! fontspec error: "font-not-found"
! 
! The font "Libertinus Serif" cannot be found.

I've checked, and the Libertinus Serif font is included in the folder texlive/texmf-dist/fonts/opentype/public/libertinus, just as it was in tex live 2017. Since this no longer compiles, I assume fontspec or xelatex has made some recent changes with respect to how it loads fonts?

EDIT:

I've installed tex live 2018 as a portable version in Windows 7 (just as I have done with every single tex live version since 2012).

If I hard code the path and the names of the individual fonts included in the tex live fonts folder, everything works fine:

\documentclass{article}

\usepackage{fontspec, lipsum}
    \setmainfont{libertinusserif-}[%
        Path = C:/texlive/texmf-dist/fonts/opentype/public/libertinus/,
        Extension = .otf,
        UprightFont = *regular,
        BoldFont = *semibold,
        ItalicFont = *italic,
        BoldItalicFont = *semibolditalic]

\begin{document}
\lipsum
\end{document}

closed as unclear what you're asking by Keks Dose, Troy, TeXnician, Phelype Oleinik, Stefan Pinnow Jun 15 '18 at 13:19

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    works ok for me. But I have windows 10 and not a portable version. What happens if you run fc-cache -fv? Does it search the texmf-tree? And does it write a cache in texmf-var\fonts\cache? – Ulrike Fischer Jun 11 '18 at 13:56
  • @UlrikeFischer 'fc-cache' is not recognized as an internal or external command, operable program or batch file. – Sverre Jun 11 '18 at 14:00
  • Did you use the texlive command line? Is fc-cache in the bin folder? – Ulrike Fischer Jun 11 '18 at 14:03
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    Ok - I renamed texlive2018 back to texlive, and now everything works. Interesting that this wasn't an issue with tex live 2017, which I also renamed texlive2017 after installing it. – Sverre Jun 11 '18 at 14:10
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    > »Hm! Does this mean that it's a problem that I have renamed the texlive folder to texlive2018?« // Really, you should have mentioned that in your question. And what I don't understand: If you renamed it, why is the path in your examples C:\texlive\..., instead of C:\texlive2018\...? – Keks Dose Jun 12 '18 at 12:46