The French forward pulled back his team into contention with two goals and two assists before Catalans beat Granada 5-3 after extra-time to win a riveting cup tie.
Real Madrid were without coach Zinedine Zidane, who continued his recovery from Covid-19, while injured captain Sergio Ramos sat in the stands wearing a mask but could still be heard yelling at his team mates and the referee.
Messi had sat out the previous two games suspended after being sent off in the Spanish Super Cup final defeat by Athletic Bilbao but looked refreshed and ultimately made the difference again.
Eden Hazard ended Real Madrid's drought in a match that coach Zinedine Zidane missed after he contracted the coronavirus.
Following a months-long national lockdown at the start of the pandemic, Spain's cultural venues reopened in the summer operating with strict capacity limitations, well-spaced seating policies and bars and cloakrooms closed.
The Society of Jesus in Spain said in a report that 81 children and 37 adult victims had been sexually abused by 96 of its members since 1927.
Images from the scene showed the walls on the top four or five storeys of the residential building in the heart of the La Latina neighbourhood had been blown out
Messi will miss Barcelona’s match against third-division club Cornella in the Copa del Rey and against Elche in La Liga.
La Liga champions top the list among Europe's major leagues with $832 million (681.2 million euros), followed by Bayern Munich, Liverpool and Paris St Germain.
Meanwhile, Lionel Messi and Antoine Griezmann each scored twice as Barcelona thrashed Granada 4-0 away to win a third consecutive La Liga game for the first time this season.
Ten provinces of central Spain were on their highest level of alert for Storm Filomena, including the capital, Madrid, where authorities have activated the red warning for the first time.
Visiting Spain for official talks, Turkey's Foreign Minister Mevlut Cavusoglu said that his country wants to resolve differences with the United States and the European Union.
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