Cyprus remain rooted to the bottom of Group E of the European qualification section for Brazil 2014 after losing in Norway last Friday and at home to Slovenia earlier this week.
And former Panathinaikos manager Nioplias has now decided to call time on his two-year spell at the helm.
"Mr Nikos Nioplias has resigned from his position as coach of the men's national team following friendly discussions," a statement from the Cypriot FA read.
"At the end of the match with Slovenia, Mr Nioplias informed the Federation of his decision to withdraw from the national team at the end of his contract in November, while offering to immediately stand down if the CFA wished so."
Nioplias expressed his dissatisfaction following Cyprus' 2-0 defeat in Oslo, admitting that his squad was too weak due to the reluctance of Cypriot clubs to blood native youngsters in their first teams.
Cypriot FA staff will take charge of those fixtures, with a new permanent coach expected to be appointed after the qualifying campaign ends.
